Search results for: dopaminergic neurons

Authors: Sun Zhe, Ruggero Micheletto

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As discussed extensively in many studies, noise in neural networks have an important role in the functioning and time evolution of the system. The mechanism by which noise induce stochastic resonance enhancing and influencing certain operations is not clarified nor is the mechanism of information storage and coding. With the present research we want to study the role of noise, especially focusing on the frequency peaks in a three variable Hindmarsh−Rose Small−World network. We investigated the behaviour of the network to external noises. We demonstrate that a variation of signal to noise ratio of about 10 dB induces an increase in membrane potential signal of about 15%, averaged over the whole network. We also considered the integral of the whole membrane potential as a paradigm of internal noise, the one generated by the brain network. We showed that this internal noise is attenuated with the size of the network or with the number of random connections. By means of Fourier analysis we found that it has distinct peaks of frequencies, moreover, we showed that increasing the size of the network introducing more neurons, reduced the maximum frequencies generated by the network, whereas the increase in the number of random connections (determined by the small-world probability p) led to a trend toward higher frequencies. This study may give clues on how networks utilize noise to alter the collective behaviour of the system in their operations.

Keywords: neural networks, stochastic processes, small-world networks, discrete Fourier analysis

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Authors: Ilzira A. Minigalieva, Tatiana V. Bushueva, Eleonore Frohlich, Vladimir Panov, Ekaterina Shishkina, Boris A. Katsnelson

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Background: The overwhelming majority of the experimental studies in the field of metal nanotoxicology have been performed on cultures of established cell lines, with very few researchers focusing on animal experiments, while a juxtaposition of conclusions inferred from these two types of research is blatantly lacking. The least studied aspect of this problem relates to characterizing and predicting the combined toxicity of metallic nanoparticles. Methods: Comparative and combined toxic effects of purposefully prepared spherical NiO and Mn₃O₄ nanoparticles (mean diameters 16.7 ± 8.2 nm and 18.4 ± 5.4 nm respectively) were estimated on cultures of human cell lines: MRC-5 fibroblasts, THP-1 monocytes, SY-SY5Y neuroblastoma cells, as well as on the latter two lines differentiated to macrophages and neurons, respectively. The combined cytotoxicity was mathematically modeled using the response surface methodology. Results: The comparative assessment of the studied NPs unspecific toxicity previously obtained in vivo was satisfactorily reproduced by the present in vitro tests. However, with respect to manganese-specific brain damage which had been demonstrated by us in animal experiment with the same NPs, the testing on neuronall cell culture showed only a certain enhancing effect of Mn₃O₄-NPs on the toxic action of NiO-NPs, while the role of the latter prevailed. Conclusion: From the point of view of the preventive toxicology, the experimental modeling of metallic NPs combined toxicity on cell cultures can give non-reliable predictions of the in vivo action’s effects.

Keywords: manganese oxide, nickel oxide, nanoparticles, in vitro toxicity

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Authors: Hassan M. H. Mustafa

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This piece of research addresses an interesting comparative analytical study. Which considers two concepts of diverse algorithmic computational intelligence approaches related tightly with Neural and Non-Neural Systems. The first algorithmic intelligent approach concerned with observed obtained practical results after three neural animal systems’ activities. Namely, they are Pavlov’s, and Thorndike’s experimental work. Besides a mouse’s trial during its movement inside figure of eight (8) maze, to reach an optimal solution for reconstruction problem. Conversely, second algorithmic intelligent approach originated from observed activities’ results for Non-Neural Ant Colony System (ACS). These results obtained after reaching an optimal solution while solving Traveling Sales-man Problem (TSP). Interestingly, the effect of increasing number of agents (either neurons or ants) on learning performance shown to be similar for both introduced systems. Finally, performance of both intelligent learning paradigms shown to be in agreement with learning convergence process searching for least mean square error LMS algorithm. While its application for training some Artificial Neural Network (ANN) models. Accordingly, adopted ANN modeling is a relevant and realistic tool to investigate observations and analyze performance for both selected computational intelligence (biological behavioral learning) systems.

Keywords: artificial neural network modeling, animal learning, ant colony system, traveling salesman problem, computational biology

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Authors: Hu-Jiang Shi, Li-Juan Zhu

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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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Authors: Keivan Jmahidi, Afshin Zahedi

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To evaluate neurotoxic effects of ACR on hypothalamus of rat, amino-cupric silver staining technique of de Olmos and electron microscopic examination were conducted. For this purpose 60 adult male Wistar rats (± 250 g) were selected. Randomly assigned groups of rats (10 rats per exposure group, as A, B, C, D, E) were exposed to 0.5, 5, 50, 100 and 500 mg/kg per day×11days i.p. respectively. The remaining 10 rats were housed in group F as control group. Control rats received daily i.p. injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, daily weight gain, gait scores and landing hindlimb foot splay (LHF) were determined. After 11 days, two rats for silver stain, and two rats for EM, were randomly selected, dissected and proper samples were collected from hypothalamus. Rats in groups D and E died within 1-2 hours due to sever toxemia. In histopathological studies no argyrophilic neurons or processes were observed in stained sections obtained from hypothalamus of rats belong to groups A, B and F, while moderate to severe argyrophilic changes were observed in different nuclei and regions of stained sections obtained from hypothalamus of rats belong to group C. In ultrastructural studies some variations in the myelin sheet of injured axons including decompactation, interlaminar space formation, disruption of the laminar sheet, accumulation of neurofilaments, vacculation and clumping inside the axolem, and finaly complete disappearance of laminar sheet were observed.

Keywords: acrylamide (ACR), amino-cupric silver staining technique of de Olmos, argyrophilia, hypothalamic neuropathy

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Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu

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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.

Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition

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Authors: Kamran Yazdanbakhsh, Somayeh Mahmoudi

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Multiple sclerosis is the most common chronic disease of the central nervous system associated with demyelination of neurons and several demyelinated parts of the disease encompasses throughout the white matter and affects the sensory and motor function. This study compared the effectiveness of two methods of cognitive therapy and supportive-expressive therapy on the efficacy and quality of life in MS patients. This is an experimental project which has used developed group pretest - posttest and follow-up with 3 groups. The study included all patients with multiple sclerosis in 2013 that were members of the MS Society of Iran in Tehran. The sample included 45 patients with MS that were selected volunteerily of members of the MS society of Iran and randomly divided into three groups and pretest, posttest, and follow-up (three months) for the three groups had been done.The dimensions of quality of life in patients with multiple sclerosis scale, and general self-efficiency scale of Schwarzer and Jerusalem was used for collecting data. The results showed that there was a significant difference between the mean of quality of life scores at pretest, posttest, and follow-up of the experimental groups. There was no significant difference between the mean of quality of life of the experimental groups which means that both groups were effective and had the same effect. There was no significant difference between the mean of self-efficiency scores in control and experimental group in pretest, posttest and follow-up. Thus, by using cognitive and supportive-expressive group therapy we can improve quality of life in MS patients and make great strides in their mental health.

Keywords: cognitive group therapy, life style, MS, self-efficiency, supportive-expressive group therapy

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: Parisa Mansour

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Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among whites. It mostly affects the lungs, causing infections and inflammation that account for 90% of deaths in CF patients. Because of this high variability in clinical presentation and organ involvement, investigating treatment responses and evaluating lung changes over time is critical to preventing CF progression. High-resolution computed tomography (HRCT) greatly facilitates the assessment of lung disease progression in CF patients. Recently, artificial intelligence was used to analyze chest CT scans of CF patients. In this paper, we propose a convolutional neural network (CNN) approach to classify CF lung patterns in HRCT images. The proposed network consists of two convolutional layers with 3 × 3 kernels and maximally connected in each layer, followed by two dense layers with 1024 and 10 neurons, respectively. The softmax layer prepares a predicted output probability distribution between classes. This layer has three exits corresponding to the categories of normal (healthy), bronchitis and inflammation. To train and evaluate the network, we constructed a patch-based dataset extracted from more than 1100 lung HRCT slices obtained from 45 CF patients. Comparative evaluation showed the effectiveness of the proposed CNN compared to its close peers. Classification accuracy, average sensitivity and specificity of 93.64%, 93.47% and 96.61% were achieved, indicating the potential of CNNs in analyzing lung CF patterns and monitoring lung health. In addition, the visual features extracted by our proposed method can be useful for automatic measurement and finally evaluation of the severity of CF patterns in lung HRCT images.

Keywords: HRCT, CF, cystic fibrosis, chest CT, artificial intelligence

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Authors: Keivan Jamshidi

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Distal swelling and eventual degeneration of axon in the CNS and PNS have been considered to be the characteristic neuropathological effects of acrylamide (ACR) neuropathy. This study was conducted to determine the neurotoxic effects of different doses of ACR (0.5, 5, 50, 100, and 500 mg/kg per day × 11days i. p.) on hypothalamus of rat using the de Olmos amino cupric-silver stain and electron microscopy. For this purpose 60 adult male rats (Wistar, approximately 250 g) were randomly assigned in 5 treatment groups as A, B, C, D, E) exposed to 0.5, 5, 50, 100, and 500 mg/kg per dayx11days i. p. and one control group as F received daily i. p. injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay were determined. After 11 days, two rats for silver stain, and two rats for EM were randomly selected; dissected and proper samples were collected from hypothalamus. Results did show no neurological behavior in groups A, B and F were observed in group C. Rats in groups D and E died within 1-2 hours due to sever toxemia. In histopathological studies based on de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from hypothalamus of rats belong to groups A, B, and F while moderate to severe argyrophilic changes were observed in different nuclei and regions of stained sections obtained from hypothalamus of rats belong to group C. In ultra-structural studies some variations in the myelin sheet of injured axons including decompactation, interlaminar space formation, disruption of the laminar sheet, accumulation of neurofilaments, vacculation, and clumping inside the axolem, and finally complete disappearance of laminar sheet were observed.

Keywords: acrylamide, hypothalamus, rat, de Olmos amino cupric, silver stain, electron microscopy

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Authors: Biruhi Tesfaye, Avinash M. Potdar

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The laboratory test process to determine the California bearing ratio (CBR) of black cotton soils is not only overpriced but also time-consuming as well. Hence advanced prediction of CBR plays a significant role as it is applicable In pavement design. The prediction of CBR of treated soil was executed by Artificial Neural Networks (ANNs) which is a Computational tool based on the properties of the biological neural system. To observe CBR values, combined eggshell and waste glass was added to soil as 4, 8, 12, and 16 % of the weights of the soil samples. Accordingly, the laboratory related tests were conducted to get the required best model. The maximum CBR value found at 5.8 at 8 % of eggshell waste glass powder addition. The model was developed using CBR as an output layer variable. CBR was considered as a function of the joint effect of liquid limit, plastic limit, and plastic index, optimum moisture content and maximum dry density. The best model that has been found was ANN with 5, 6 and 1 neurons in the input, hidden and output layer correspondingly. The performance of selected ANN has been 0.99996, 4.44E-05, 0.00353 and 0.0067 which are correlation coefficient (R), mean square error (MSE), mean absolute error (MAE) and root mean square error (RMSE) respectively. The research presented or summarized above throws light on future scope on stabilization with waste glass combined with different percentages of eggshell that leads to the economical design of CBR acceptable to pavement sub-base or base, as desired.

Keywords: CBR, artificial neural network, liquid limit, plastic limit, maximum dry density, OMC

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Authors: Luis C. Parra

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The significant wave height prediction is an issue of great interest in the field of coastal activities because of the non-linear behavior of the wave height and its complexity of prediction. This study aims to present a machine learning model to forecast the significant wave height of the oceanographic wave measuring buoys anchored at Mooloolaba of the Queensland Government Data. Modeling was performed by a multilayer perceptron neural network-genetic algorithm (GA-MLP), considering Relu(x) as the activation function of the MLPNN. The GA is in charge of optimized the MLPNN hyperparameters (learning rate, hidden layers, neurons, and activation functions) and wrapper feature selection for the window width size. Results are assessed using Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE). The GAMLPNN algorithm was performed with a population size of thirty individuals for eight generations for the prediction optimization of 5 steps forward, obtaining a performance evaluation of 0.00104 MSE, 0.03222 RMSE, 0.02338 MAE, and 0.71163% of MAPE. The results of the analysis suggest that the MLPNNGA model is effective in predicting significant wave height in a one-step forecast with distant time windows, presenting 0.00014 MSE, 0.01180 RMSE, 0.00912 MAE, and 0.52500% of MAPE with 0.99940 of correlation factor. The GA-MLP algorithm was compared with the ARIMA forecasting model, presenting better performance criteria in all performance criteria, validating the potential of this algorithm.

Keywords: significant wave height, machine learning optimization, multilayer perceptron neural networks, evolutionary algorithms

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Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

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The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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Authors: Ahmed R. Z. Baghdadi, Ibrahim M. I. Hamoda,  Mona H. Gamal Eldein, Ibrahim Magdy Elnaggar

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Background: High-velocity low amplitude thrust (HVLAT) manipulation and low-velocity low amplitude (LVLA) mobilization are an effective treatment for low back pain (LBP). Purpose: This study compared the effects of HVLAT versus LVLA on pain, functional deficits and segmental mobility in treatment of chronic mechanical LBP. Methods: Ninety patients suffering from chronic mechanical LBP are classified to three groups; Thirty patients treated by HVLAT (group I), thirty patients treated by LVLA (group II) and thirty patients as control group (group III) participated in the study. The mean age was 28.00±2.92, 27.83±2.28 and 28.07±3.05 years and BMI 27.98±2.60, 28.80±2.40 and 28.70±2.53 kg/m2 for group I, II and III respectively. The Visual Analogue Scale (VAS), the Oswestry low back pain disability questionnaire and modified schoper test were used for assessment. Assessments were conducted two weeks before and after treatment with the control group being assessed at the same time intervals. The treatment program group one was two weeks single session per week, and for group II two sessions per week for two weeks. Results: The One-way ANOVA revealed that group I had significantly lower pain scores and Oswestry score compared with group II two weeks after treatment. Moreover, the mobility in modified schoper increased significantly and the pain scores and Oswestry scores decreased significantly after treatment in group I and II compared with control group. Interpretation/Conclusion: HVLAT is preferable to LVLA mobilization, possibly due to a beneficial neurophysiological effect by Stimulating mechanically sensitive neurons in the lumbar facet joint capsule.

Keywords: low back pain, manipulation, mobilization, low velocity

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: Parisa Mansour

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Understanding how vision works in both health and disease involves understanding the anatomy and physiology of the eye as well as the neural pathways involved in visual perception. The development of imaging techniques for the visual system is essential for understanding the neural foundation of visual function or impairment. MRI provides a way to examine neural circuit structure and function without invasive procedures, allowing for the detection of brain tissue abnormalities in real time. One of the advanced MRI methods is manganese-enhanced MRI (MEMRI), which utilizes active manganese contrast agents to enhance brain tissue signals in T1-weighted imaging, showcasing connectivity and activity levels. The way manganese ions build up in the eye, and visual pathways can be due to their spread throughout the body or by moving locally along axons in a forward direction and entering neurons through calcium channels that are voltage-gated. The paramagnetic manganese contrast is utilized in MRI for various applications in the visual system, such as imaging neurodevelopment and evaluating neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this assessment, we outline four key areas of scientific research where MEMRI can play a crucial role - understanding brain structure, mapping nerve pathways, monitoring nerve cell function, and distinguishing between different types of glial cell activity. We discuss various studies that have utilized MEMRI to investigate the visual system, including delivery methods, spatiotemporal features, and biophysical analysis. Based on this literature, we have pinpointed key issues in the field related to toxicity, as well as sensitivity and specificity of manganese enhancement. We will also examine the drawbacks and other options to MEMRI that could offer new possibilities for future exploration.

Keywords: glial activity, manganese-enhanced magnetic resonance imaging, neuroarchitecture, neuronal activity, neuronal tract tracing, visual pathway, eye

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Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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Authors: Yong Chen

Abstract:

To understand the detailed molecular mechanisms of memory formation in engram cells is one of the most fundamental questions in neuroscience. Recent single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) techniques have allowed us to explore the sparsely activated engram ensembles, enabling access to the molecular mechanisms that underlie experience-dependent memory formation and consolidation. However, the absence of specific and powerful computational methods to detect memory-related genes (modules) and their regulatory relationships in the sc/snRNA-seq datasets has strictly limited the analysis of underlying mechanisms and memory coding principles in mammalian brains. Here, we present a deep-learning method named SCENTBOX, to detect memory-related gene modules and causal regulatory relationships among themfromsc/snRNA-seq datasets. SCENTBOX first constructs codifferential expression gene network (CEGN) from case versus control sc/snRNA-seq datasets. It then detects the highly correlated modules of differential expression genes (DEGs) in CEGN. The deep network embedding and attention-based convolutional neural network strategies are employed to precisely detect regulatory relationships among DEG genes in a module. We applied them on scRNA-seq datasets of TRAP; Ai14 mouse neurons with fear memory and detected not only known memory-related genes, but also the modules and potential causal regulations. Our results provided novel regulations within an interesting module, including Arc, Bdnf, Creb, Dusp1, Rgs4, and Btg2. Overall, our methods provide a general computational tool for processing sc/snRNA-seq data from case versus control studie and a systematic investigation of fear-memory-related gene modules.

Keywords: sc/snRNA-seq, memory formation, deep learning, gene module, causal inference

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Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

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Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

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Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: drug addiction, artificial neural networks, multilayer perceptron (MLP), decision support system

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Authors: Amal Shehata

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Low back pain related to disc prolapse is localized in the lumbar area and it may be radiated to the lower extremities, starting from neurons near or around the spinal canal. Most of the population may be affected with disc prolapse within their lifetime and leads to lost productivity, disability and loss of function. The study purpose was to examine the effect of rehabilitative nursing program on pain intensity and functional status among patients with discectomy. Design: Aquasi experimental design was utilized. Setting: The study was carried out at neurosurgery department and out patient's clinic of Menoufia University and Teaching hospitals at Menoufia governorate, Egypt. Instrument of the study: Five Instruments were used for data collection: Structured interviewing questionnaire, Functional assessment instrument, Observational check list, Numeric rating Scale and Oswestry low back pain disability questionnaire. Results: There was an improvement in mean total knowledge score about disease process, discectomy and rehabilitation program in study group (25.32%) than control group (7.32%). There was highly statistically significant improvement in lumbar flexibility among study group (80%) than control group (30%) after rehabilitation program than before. Also there was a decrease in pain score in study group (58% no pain) than control group (28% no pain) after rehabilitation program. There was an improvement in total disability score of study group (zero %) regarding effect of pain on the activity of daily living after rehabilitation program than control group (16%). Conclusion: Application of rehabilitative nursing program for patient with discectomy had proven a positive effect in relation to knowledge score, pain reduction, activity of daily living and functional abilities. Recommendation: A continuous rehabilitative nursing program should be carried out for all patients immediately after discectomy surgery on regular basis. Also A colored illustrated booklet about rehabilitation program should be available and distributed for all patients before surgery.

Keywords: discectomy, rehabilitative nursing program, pain intensity, functional status

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Authors: Velimir "monty" Vesselinov, Trais Kliplhuis, Hope Jasperson

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Artificial intelligence (AI) is a powerful tool in the geothermal energy sector, aiding in both exploration and utilization. Identifying promising geothermal sites can be challenging due to limited surface indicators and the need for expensive drilling to confirm subsurface resources. Geothermal reservoirs can be located deep underground and exhibit complex geological structures, making traditional exploration methods time-consuming and imprecise. AI algorithms can analyze vast datasets of geological, geophysical, and remote sensing data, including satellite imagery, seismic surveys, geochemistry, geology, etc. Machine learning algorithms can identify subtle patterns and relationships within this data, potentially revealing hidden geothermal potential in areas previously overlooked. To address these challenges, a SIML (Science-Informed Machine Learning) technology has been developed. SIML methods are different from traditional ML techniques. In both cases, the ML models are trained to predict the spatial distribution of an output (e.g., pressure, temperature, heat flux) based on a series of inputs (e.g., permeability, porosity, etc.). The traditional ML (a) relies on deep and wide neural networks (NNs) based on simple algebraic mappings to represent complex processes. In contrast, the SIML neurons incorporate complex mappings (including constitutive relationships and physics/chemistry models). This results in ML models that have a physical meaning and satisfy physics laws and constraints. The prototype of the developed software, called GeoTGO, is accessible through the cloud. Our software prototype demonstrates how different data sources can be made available for processing, executed demonstrative SIML analyses, and presents the results in a table and graphic form.

Keywords: science-informed machine learning, artificial inteligence, exploration, utilization, hidden geothermal

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Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto

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Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.

Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone

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Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

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Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

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Authors: Afshin Zahedi, Keivan Jamshidi

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This study was conducted to determine the neurotoxic effects of different doses of ACR on the thoracic axons of the spinal cord of rat. To evaluate this hypothesis in the thoracic axons, amino-cupric silver staining technique of the de Olmos was conducted to define the histopathologic characteristic (argyrophilia) of axonal damage following ACR exposure. For this purpose 60 adult male rats (Wistar, approximately 250 g) were selected. Rats were hosed in polycarbonate boxes as two per each. Randomly assigned groups of rats (10 rats per exposure group, total 5 exposure groups as A, B, C, D and E) were exposed to 0.5, 5, 50, 100 and 500 mg/kg per day×11days intraperitoneal injection (IP injection) respectively. The remaining 10 rats were housed in group (F) as control group. Control rats received daily injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay (LHF) were determined. Weight gains were measured daily prior to injection. Gait scoring involved observation of spontaneous open field locomotion, included evaluations of ataxia, hopping, rearing and hind foot placement, and hindlimb foot splay were determined 3-4 times per week. Gait score was assigned from 1-4. After 11 days, two rats for silver stain, were randomly selected, dissected and proper samples were collected from thoracic portion of the spinal cord of rat. Results did show no neurological behavior in groups A, B and F, whereas severe neurotoxicity was observed in groups C and D. Rats in groups E died within 1-2 hours due to severe toxemia. In histopathological studies based on the de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups A, B and F, while moderate to severe argyrophilic changes were observed in different stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups C and D.

Keywords: acrylamide, rat, axonopathy, argyrophily, de Olmos

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Authors: Mohammad M. Aria, Fatma Öz, Yashar Esmaeilian, Marco Carofiglio, Valentina Cauda, Özlem Yalçın

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Photoelectrical stimulation of cells with semiconductor organic polymers have been shown promising applications in neuroprosthetics such as retinal prosthesis. Photoelectrical stimulation of the cell membranes can be induced through a photo-electric charge separation mechanism in the semiconductor materials, and it can alter intracellular calcium level through both stimulation of voltage-gated ion channels and increase of intracellular reactive oxygen species (ROS) level. On the other hand, targeting voltage-gated ion channels in cancer cells to induce cell apoptosis through calcium signaling alternation is an effective mechanism which has been explained before. In this regard, remote control of the voltage-gated ion channels aimed to alter intracellular calcium by using photo-active organic polymers can be novel technology in cancer therapy. In this study, we used P (ITO/Indium thin oxide)/P3HT(poly(3-hexylthiophene-2,5-diyl)) and PN (ITO/ZnO/P3HT) photovoltaic junctions to stimulate MDA-MB-231 breast cancer cells. We showed that the photo-stimulation of breast cancer cells through photo capacitive current generated by the photovoltaic junctions are able to excite the cells and alternate intracellular calcium based on the calcium imaging (at 8mW/cm² green light intensity and 10-50 ms light durations), which has been reported already to safety stimulate neurons. The control group did not undergo light treatment and was cultured in T-75 flasks. We detected 20-30% cell death for ITO/P3HT and 51-60% cell death for ITO/ZnO/P3HT samples in the light treated MDA-MB-231 cell group. Western blot analysis demonstrated poly(ADP-ribose) polymerase (PARP) activated cell death in the light treated group. Furthermore, Annexin V and PI fluorescent staining indicated both apoptosis and necrosis in treated cells. In conclusion, our findings revealed that the photoelectrical stimulation of cells (through long time overstimulation) can induce cell death in cancer cells.

Keywords: Ca²⁺ signaling, cancer therapy, electrically excitable cells, photoelectrical stimulation, voltage-gated ion channels

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Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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Authors: Sunidhi Syal, Rasangi Tennakoon, Patrick O'Donoghue

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Polyglutamine (polyQ) diseases are a group of diseases related to neurodegeneration caused by repeats of the amino acid glutamine (Q) in the DNA, which translates into an elongated polyQ tract in the protein. The pathological explanation is that the polyQ tract forms cytotoxic aggregates in the neurons, leading to their degeneration. There are no cures or preventative efforts established for these diseases as of today, although the symptoms of these diseases can be relieved. This study specifically focuses on Huntington's disease, which is a type of polyQ disease in which aggregation is caused by the extended cytosine, adenine, guanine (CUG) codon repeats in the huntingtin (HTT) gene, which encodes for the huntingtin protein. Using this principle, we attempted to create six models, which included mutating wildtype tRNA alanine variant tRNA-AGC-8-1 to have glutamine anticodons CUG and UUG so serine is incorporated at glutamine sites in poly Q tracts. In the process, we were successful in obtaining tAla-8-1 CUG mutant clones in the HTTexon1 plasmids with a polyQ tract of 23Q (non-pathogenic model) and 74Q (disease model). These plasmids were transfected into mouse neuroblastoma cells to characterize protein synthesis and aggregation in normal and mistranslating cells and to investigate the effects of glutamines replaced with alanines on the disease phenotype. Notably, we observed no noteworthy differences in mean fluorescence between the CUG mutants for 23Q or 74Q; however, the Triton X-100 assay revealed a significant reduction in insoluble 74Q aggregates. We were unable to create a tAla-8-1 UUG mutant clone, and determining the difference in the effects of the two glutamine anticodons may enrich our understanding of the disease phenotype. In conclusion, by generating structural disruption with the amino acid alanine, it may be possible to find ways to minimize the toxicity of Huntington's disease caused by these polyQ aggregates. Further research is needed to advance knowledge in this field by identifying the cellular and biochemical impact of specific tRNA variants found naturally in human genomes.

Keywords: Huntington's disease, polyQ, tRNA, anticodon, clone, overlap PCR

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