ATR-IR Study of the Mechanism of Aluminum Chloride Induced Alzheimer’s Disease; Curative and Protective Effect of Lipidium sativum Water Extract on Hippocampus Rats Brain Tissue

Authors: Maha Jameal Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad Shaker Ali

Abstract:

The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width (HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder, and decreasing in lipid polarity in AlCl3 group indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approached nearly the control values. These results supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. In addition, the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: Aluminum chloride, Alzheimer’s disease, ATR-IR, Lipidium sativum.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1110153

References:

[1] N. A. Yassin, S. M. El-Shenawy, K. A. Mahdy, N. A. Gouda, A. E. Marrie, A. R. Farrag, and B. M. Ibrahim, "Effect of Boswellia serrata on Alzheimer’s disease induced in rats," J Arab Soc Med Res, vol. 8, pp. 1- 11, March 2013.
[2] Alzheimer's-Association, "2014 Alzheimer's disease facts and figures," Alzheimer's & Dementia, vol. 10, no. 2, pp. e47-e92, March 2014.
[3] Alzheimer’s Disease International. About Alzheimer’s disease. (Accessed December 14, (2005) at http://www.alz.co.uk/ alzheimers/faq.html#howmany).
[4] N. Braidy, A. Poljak, C. Marjo, H. Rutlidge, A. Rich, T. Jayasena, N. C. Inestrosa, and P. Sachdev, "Metal and complementary molecular bioimaging in Alzheimer's disease," Front Aging Neurosci., vol. 6, no. 138, pp. 1-14, July 2014.
[5] Bukowska, "Toxicity of 2, 4-dichlorophenoxyacetic acid – molecular mechanisms," Polish J. of Environ. Stud., vol. 15, no. 3, pp. 365-374, 2006.
[6] G. Cakmak, F. Zorlu, M. Severcan, and F. Severcan, "Screening of protective effect of amifostine on radiation-induced structural and functional variations in rat liver microsomal membranes by FT-IR spectroscopy," Analytical chemistry, vol. 83, no. 7, pp. 2438-2444, 2011.
[7] M. Kawahara and M. Kato-Negishi, "Link between aluminum and the pathogenesis of Alzheimer's disease: the integration of the aluminum and amyloid cascade hypotheses," International Journal of Alzheimer’s Disease, vol. 2011, pp. 1-17, January 2011.
[8] A. Shati, F. G. Elsaid, and E. E. Hafez, "Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup," Neuroscience, vol. 175, no. null, pp. 66-74, 2011.
[9] P. Sethi, A. Jyoti, R. Singh, E. Hussain, and D. Sharma, "Aluminiuminduced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats," NeuroToxicology, vol. 29, no. 6, pp. 1069–1079, November 2008.
[10] P. Y. Niu, Q. Niu, Q. L. Zhang, L. P. Wang, S. E. He, T. C. Wu, P. Conti, M. Di-Gioacchino, and P. Boscolo, "uminum impairs rat neural cell mitochondria in vitro," Int. J. Immunopathol. Pharmacol, vol. 18, pp. 683–689, October 2005.
[11] Kumar, A. Bal, and K. D. Gill, "Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium," Brain Res., vol. 1232, no., pp. 94–103, September 2008.
[12] V. Kumar, A. Bal, and K. D. Gill, "Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage," Toxicology, vol. 255, no. 3, pp. 117–123, January 2009.
[13] V. Kumar, A. Bal, and K. D. Gill, "Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain," Toxicology, vol. 264, no. 3, pp. 137–144, October 2009.
[14] J. L. Esparza, M. Gómez, M. Rosa Nogues, J. L. Paternain, J. Mallol, and J. L. Domingo, "Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum exposed rats," Journal of pineal research, vol. 39, no. 2, pp. 129-136, September 2005.
[15] H. C. Lee and Y. H. Wei, "Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging," Experimental biology and medicine, vol. 232, no. 5, pp. 592-606, May 2007.
[16] A. Moshtaghie, "Aluminium administration on acetylcholinesterase activity of different regions of rat brain," Med J Islamic Acad Sci, vol. 12, pp. 105–108, 1999.
[17] Szutowiicz, H. Bielarcczyk, Y. Kisielevski, A. Jankowska, B. Madziar, and M. Tomaszewicz, "Effects of aluminium and calcium on acetyl-CoA metabolism in rat brain mitochondria," J Neurochem, vol. 71, no. 6, pp. 2447–2453, December 1998.
[18] R. Pan, S. Qiu, D. X. Lu, and J. Dong, "Curcumin improves learning and memory ability and its neuroprotective mechanism in mice," Chinese Medical Journal (English Edition), vol. 121, no. 9, pp. 832-839, 2008.
[19] L. A. Daiello, E. K. Festam, B. R. Ott, and W. C. Heindel, "Cholinesterase inhibitors improve visual attention in drivers with Alzheimer’s disease," Alzheimers Dement, vol. 4, no. 4, pp. T498, 2008.
[20] F. Conforti, S. Sosa, M. Marrelli, F. Menichini, G. A. Statti, D. Uzunov, A. Tubaro, and F. Menichini, "The protective ability of mediterranean dietary plants against the oxidative damage: The role of radical oxygen species in inflammation and the polyphenol, flavonoid and sterol contents," Food Chemistry, vol. 112, no. 3, pp. 587-594, February 2009.
[21] S. R. Mentreddy, "Medicinal plant species with potential antidiabetic properties. Journal of the Science of Food and Agriculture," Journal of the Science of Food and Agriculture, vol. 87, no. 5, pp. 743-750, April 2007.
[22] R. Drury and E. Wallington, Carleton’s histological technique, 5th ed. Oxford: Oxford University Press, 1980, pp. 188–291.
[23] J. D. Banchroft, A. Stevens, and D. R. Turner, Theory and Practice of Histological Techniques, 4th ed. New York: Churchill Livingstone, 1996.
[24] V. Kumar and K. D. Gill, "Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its amelioration: a review," NeuroToxicology, vol. 41, pp. 154-166, March 2014.
[25] H. L. Casal and H. H. Mantsch, "Polymorphic phase behaviour of phospholipid membranes studied by infrared spectroscopy," Biochim Biophys Acta, vol. 779, no. 4, pp. 381-401, December 1984.
[26] P. Axelsen, H. Komatsu, and I. Murray, "oxidative stress and cell membranes in the pathogenesis of Alzheimer's disease," Physiology, vol. 26, no. 1, pp. 54-69, February 2011.
[27] Gella and I. Bolea, "Oxidative stress in Alzheimer's disease: pathogenesis, biomarkers and therapy," in Alzheimer's disease pathogenesis-core concepts, shifting paradigms and therapeutic targets, Rijeka, Croatia: InTech, 2011, pp. 319-344.
[28] N. S. Selim, O. S. Desouky, N. M. smail, and A. Z. Dakrory, "Spectroscopic analysis of irradiated erythrocytes," Radiation Physics and Chemistry, vol. 80, no. 12, pp. 1337-1342, December 2011.
[29] G. Cakmak, L. M. Miller, F. Zorlu, and F. Severcan, "Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study," Archives of biochemistry and biophysics, vol. 520, no. 2, pp. 67-73, April 2012.
[30] S. Khouw, S. Parthasarathy, and J. L. Witztum, "Radioiodination of low density lipoprotein initiates lipid peroxidation: protection by use of antioxidants," Journal of lipid research, vol. 34, no. 9, pp. 1483-1496, September 1993.
[31] L. L. de Zwart, J. H. Meerman, J. N. Commandeur, and N. P. Vermeulen, "Biomarkers of free radical damage: applications in experimental animals and in humans," Free Radical Biology and Medicine, vol. 26, no. 1-2, pp. 202-226, January 1999.
[32] K. Z. Liu, R. Bose, and H. H. Mantsch, "Infrared spectroscopic study of diabetic platelets," Vibrational spectroscopy, vol. 28, no. 1, pp. 131-136, February 2002.
[33] H. Yin, L. Xu, and N. A. Porter, "Free radical lipid peroxidation: mechanisms and analysis," Chemical reviews, vol. 111, no. 10, pp. 5944-5972, August 2011.
[34] O. P. Lamba, M. C. Y. Sundeep Lal, M. F. Lou, and D. Borchman., "Spectroscopic detection of lipid peroxidation products and structural changes in a sphingomyelin model system," Biochimica et Biophysica Acta, vol. 1081, no. 2, pp. 181-187, January 1991.
[35] M. V. Fraile, B. Patrón-Gallardo, G. López-Rodríguez, and P. Carmonab, "FT-IR study of multilamellar lipid dispersions containing cholesteryl linoleate and dipalmitoylphosphatidylcholine," Chemistry and Physics of Lipids, vol. 97, no. 2, pp. 119-128, February 1999.
[36] Borchman, F. Giblin, V. Leverenz, V. Reddy, L. Li-Ren, M. Yappert, D. Tang, and L. Li, "Impact of aging and hyperbaric oxygen in vivo on guinea pig lens lipids and nuclear light scatter," Invest Ophthalmol Vis Sci., vol. 41, no. 10, pp. 3061–3073, September 2000.
[37] Borchman, G. N. Foulks, M. C. Yappert, J. Bell, E. Wells, S. Neravetla, and V. Greenstone, "Human meibum lipid conformation and thermodynamic changes with meibomian-gland dysfunction," Investigative ophthalmology & visual science, vol. 52, no. 6, pp. 3805– 3817, May 2011.
[38] N. Arispe, E. Rojas, and H. B. Pollard, "Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum," Proceedings of the National Academy of Sciences, vol. 90, no. 2, pp. 567–571, January 1993
[39] J. McLaurin and A. Chakrabartty, "Membrane disruption by alzheimer β-amyloid peptides mediated through specific binding to either phospholipids or gangliosides implications for neurotoxicity," Journal of Biological Chemistry, vol. 271, pp. 26482-26489, October 1996
[40] H. Hartmann, A. Eckert, and W. E. Muller, "Apolipoprotein E and cholesterol affect neuronal calcium signaling: the possible relationship to β-amyloid neurotoxicity," Biochemical and biophysical research communications, vol. 200, no. 3, pp. 1185-1192, May 1994.
[41] L. M. Miller, M. W. Bourassa, and R. J. Smith, "FTIR spectroscopic imaging of protein aggregation in living cells," Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1828, no. 10, pp. 2339-2346, October 2013.
[42] V. Koppaka and P. H. Axelsen, "Accelerated accumulation of amyloid β proteins on oxidatively damaged lipid membranes," Biochemistry, vol. 39, no. 32, pp. 10011-10016, August 2000.
[43] M. A. Lovell, W. D. Ehmann, S. M. Butler, and W. R. Markesbery, "Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease," Neurology, vol. 45, no. 8, pp. 1594-1601, August 1995.
[44] M. Ramirez-Alvarado, J. W. Kelly, and C. M. Dobson, Protein misfolding diseases: Current and emerging principles and therapies vol. 14. New York: John Wiley & Sons, 2010.
[45] N. A. Avdulov, S. V. Chochina, U. Igbavboa, E. O. O'Hare, F. Schroeder, J. P. Cleary, and W. G. Wood, "Amyloid β-Peptides Increase Annular and Bulk Fluidity and Induce Lipid Peroxidation in Brain Synaptic Plasma Membranes," Journal of neurochemistry, vol. 68, no. 5, pp. 2086-2091, May 1997.
[46] S. V. Chochina, N. A. Avdulov, U. Igbavboa, J. P. Cleary, E. O. O'Hare, and W. G. Wood, "Amyloid β-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region," Journal of lipid Research, vol. 42, no. 8, pp. 1292-1297, August 2001.
[47] T. L. Spires and B. T. Hyman, "Neuronal structure is altered by amyloid plaques," Rev. Neurosci, vol. 15, no. 4, pp. 267–278, August 2004.
[48] J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N Y Acad. Sci., vol. 1097, pp. 30–39, February 2007.
[49] D. L. Moolman, O. V. Vitolo, J. P. Vonsattel, and M. L. Shelanski, "Dendrite and dendritic spine alterations in Alzheimer models," J. Neurocytol, vol. 33, no. 3, pp. 377–387, May 2004.
[50] J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches," Nat. Neurosci, vol. 7, pp. 1181–1183, October 2004.
[51] Z. Šišková, D. Justus, H. Kaneko, D. Friedrichs, N. Henneberg, T. Beutel, J. Pitsch, S. Schoch, A. Becker, H. v. d. Kammer, and S. RemyRemy, "Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer’s disease," Neuron, vol. 84, no. 5, pp. 1023-1033, December 2014.
[52] D. Johnston, J. C. Magee, C. M. Colbert, and B. R. Cristie, "Activeproperties of neuronal dendrites," Annu. Rev. Neurosci, vol. 19, no., pp. 165–186, 1996.
[53] J. J. Palop, J. Chin, E. D. Roberson, J. Wang, M. T. Thwin, N. Bien-Ly, J. Yoo, K. O. Ho, G. Q. Yu, A. Kreitzer, S. Finkbeiner, J. L. Noebels, and L. Mucke, "Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease," Neuron, vol. 55, no. 5, pp. 697–711, September 2007.
[54] M. A. Busche, G. Eichhoff, H. Adelsberger, D. Abramowski, K. H. Wiederhold, C. Haass, M. Staufenbiel, A. Konnerth, and O. Garaschuk, "Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer’s disease," Science, vol. 321, no. 5896, pp. 1686–1689, September 2008.
[55] P. E. Sanchez, L. Zhu, L. Verret, K. A. Vossel, A. G. Orr, J. R. Cirrito, N. Devidze, K. Ho, G. Q. Yu, J. J. Palop, and L. Mucke, "Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model," Proc. Natl. Acad. Sci. USA vol. 109, no. 42, pp. E2895–E2903, October 2012
[56] K. A. Vossel, A. J. Beagle, G. D. Rabinovici, H. Shu, S. E. Lee, G. Naasan, M. Hegde, S. B. Cornes, M. L. Henry, A. B. Nelson, W. W. Seeley, M. D. Geschwind, M. L. Gorno-Tempini, T. Shih, H. E. Kirsch, P. A. Garcia, B. L. Miller, and L. Mucke, "Seizures and epileptiform activity in the early stages of Alzheimer disease," J. Am. Med. Assoc. neurology, vol. 70, no. 9, pp. 1158–1166, September 2013.
[57] M. A. Busche, X. Chen, H. A. Henning, J. Reichwald, M. Staufenbiel, B. Sakmann, and A. Konnerth, "Critical role of soluble amyloid-b for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease," Proc. Natl. Acad. Sci. USA, vol. 109, no. 22, pp. 8740–8745, May 2012.