Login Register Cart 0
Generic placeholder image

Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Ameliorative Effect of Acetyl L-carnitine in Alzheimer's Disease via Downregulating of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive Deficit in Mouse Model

Author(s): Nisha Verma, Jeetendra Kumar Gupta, Krishna Kumar Varshney and Rajnish Srivastava*

Volume 14, Issue 3, 2021

Published on: 21 December, 2021

Page: [219 - 231] Pages: 13

DOI: 10.2174/1872312814666211209102136

Price: $65

Abstract

Aims: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model.

Background: Alzheimer’s disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD.

Objective: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer’s disease (AD) in the mouse model.

Materials and Methods: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+ SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α.

Results: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice.

Conclusion: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC's potential to be used as a supplementation in the pharmacotherapy of AD.

Keywords: Acetyl L-carnitine, methyl donor, sodium orthovanadate, hyperhomocysteinemia, alzheimer’s disease, prefrontal cortex.

« Previous Next »
Graphical Abstract

[1]
Kelley, B.J.; Petersen, R.C. Alzheimer’s disease and mild cognitive impairment. Neurol. Clin., 2007, 25(3), 577-609.
[http://dx.doi.org/10.1016/j.ncl.2007.03.008] [PMID: 17659182]
[2]
Varshney, K.K.; Gupta, J.K.; Mujwar, S. Homocysteine induced neurological dysfunctions: A link to neurodegenerative disorders. Int. J. Med. Res. Health Sci., 2019, 8, 135-146.
[3]
Patterson, C. World alzheimer report. 2018.
[4]
Grimm, A.; Mensah-Nyagan, A.G.; Eckert, A. Alzheimer, mitochondria and gender. Neurosci. Biobehav. Rev., 2016, 67, 89-101.
[http://dx.doi.org/10.1016/j.neubiorev.2016.04.012] [PMID: 27139022]
[5]
Lian, W.; Fang, J.; Xu, L.; Zhou, W.; Kang, D.; Xiong, W.; Jia, H.; Liu, A.L.; Du, G.H. DL0410 ameliorates memory and cognitive impairments induced by scopolamine via increasing cholinergic neurotransmission in mice. Molecules, 2017, 22(3), 410.
[http://dx.doi.org/10.3390/molecules22030410] [PMID: 28272324]
[6]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the cholinergic system. Curr. Neuropharmacol., 2016, 14(1), 101-115.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[7]
Ballinger, E.C.; Ananth, M.; Talmage, D.A.; Role, L.W. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron, 2016, 91(6), 1199-1218.
[http://dx.doi.org/10.1016/j.neuron.2016.09.006] [PMID: 27657448]
[8]
Hasselmo, M.E.; Wyble, B.P.; Wallenstein, G.V. Encoding and retrieval of episodic memories: Role of cholinergic and GABAergic modulation in the hippocampus. Hippocampus, 1996, 6(6), 693-708.
[http://dx.doi.org/10.1002/(SICI)1098-1063(1996)6:6<693::AID-HIPO12>3.0.CO;2-W] [PMID: 9034856]
[9]
Maurer, S.V.; Williams, C.L. The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Front. Immunol., 2017, 8, 1489.
[http://dx.doi.org/10.3389/fimmu.2017.01489] [PMID: 29167670]
[10]
Agis-Torres, A.; Sölhuber, M.; Fernandez, M.; Sanchez-Montero, J.M. Multi-target-directed ligands and other therapeutic strategies in the search of a real solution for Alzheimer’s disease. Curr. Neuropharmacol., 2014, 12(1), 2-36.
[http://dx.doi.org/10.2174/1570159X113116660047] [PMID: 24533013]
[11]
Wang, Y.; Wang, H.; Chen, H.Z. AChE inhibition-based multi-target-directed ligands, a novel pharmacological approach for the symptomatic and disease-modifying therapy of Alzheimer’s disease. Curr. Neuropharmacol., 2016, 14(4), 364-375.
[http://dx.doi.org/10.2174/1570159X14666160119094820] [PMID: 26786145]
[12]
Abdul Manap, A.S.; Wei Tan, A.C.; Leong, W.H.; Yin Chia, A.Y.; Vijayabalan, S.; Arya, A.; Wong, E.H.; Rizwan, F.; Bindal, U.; Koshy, S.; Madhavan, P. Synergistic effects of curcumin and piperine as potent acetylcholine and amyloidogenic inhibitors with significant neuroprotective activity in SH-SY5Y cells via computational molecular modeling and in vitro assay. Front. Aging Neurosci., 2019, 11, 206.
[http://dx.doi.org/10.3389/fnagi.2019.00206] [PMID: 31507403]
[13]
Ho, P.I.; Ortiz, D.; Rogers, E.; Shea, T.B. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. J. Neurosci. Res., 2002, 70(5), 694-702.
[http://dx.doi.org/10.1002/jnr.10416] [PMID: 12424737]
[14]
McCaddon, A.; Davies, G.; Hudson, P.; Tandy, S.; Cattell, H. Total serum homocysteine in senile dementia of Alzheimer type. Int. J. Geriatr. Psychiatry, 1998, 13(4), 235-239.
[http://dx.doi.org/10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8] [PMID: 9646150]
[15]
Morris, M.S. Homocysteine and Alzheimer’s disease. Lancet Neurol., 2003, 2(7), 425-428.
[http://dx.doi.org/10.1016/S1474-4422(03)00438-1] [PMID: 12849121]
[16]
Xie, F.; Zhao, Y.; Ma, J.; Gong, J.B.; Wang, S.D.; Zhang, L.; Gao, X.J.; Qian, L.J. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats. Cell Stress Chaperones, 2016, 21(5), 915-926.
[http://dx.doi.org/10.1007/s12192-016-0718-0] [PMID: 27435080]
[17]
Mahaman, Y.A.R.; Huang, F.; Wu, M.; Wang, Y.; Wei, Z.; Bao, J.; Salissou, M.T.M.; Ke, D.; Wang, Q.; Liu, R.; Wang, J.Z.; Zhang, B.; Chen, D.; Wang, X. Moringa oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments. J. Alzheimers Dis., 2018, 63(3), 1141-1159.
[http://dx.doi.org/10.3233/JAD-180091] [PMID: 29710724]
[18]
Zeng, P.; Shi, Y.; Wang, X.M.; Lin, L.; Du, Y.J.; Tang, N.; Wang, Q.; Fang, Y.Y.; Wang, J.Z.; Zhou, X.W.; Lu, Y.; Tian, Q. Emodin rescued hyperhomocysteinemia-induced dementia and alzheimer’s disease-like features in rats. Int. J. Neuropsychopharmacol., 2019, 22(1), 57-70.
[http://dx.doi.org/10.1093/ijnp/pyy090] [PMID: 30407508]
[19]
Aureli, T.; Miccheli, A.; Ricciolini, R.; Di Cocco, M.E.; Ramacci, M.T.; Angelucci, L.; Ghirardi, O.; Conti, F. Aging brain: Effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res., 1990, 526(1), 108-112.
[http://dx.doi.org/10.1016/0006-8993(90)90255-A] [PMID: 2078811]
[20]
Goo, M.J.; Choi, S.M.; Kim, S.H.; Ahn, B.O. Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats. Arch. Pharm. Res., 2012, 35(1), 145-154.
[http://dx.doi.org/10.1007/s12272-012-0116-9] [PMID: 22297753]
[21]
Onger, M.E.; Kaplan, S.; Deniz, O.G.; Altun, G.; Altunkaynak, B.Z.; Balcı, K.; Raimondo, S.; Geuna, S. Possible promoting effects of melatonin, leptin and alcar on regeneration of the sciatic nerve. J. Chem. Neuroanat., 2017, 81, 34-41.
[http://dx.doi.org/10.1016/j.jchemneu.2017.02.003] [PMID: 28163216]
[22]
Barhwal, K.; Hota, S.K.; Prasad, D.; Singh, S.B.; Ilavazhagan, G. Hypoxia-induced deactivation of NGF-mediated ERK1/2 signaling in hippocampal cells: Neuroprotection by acetyl-L-carnitine. J. Neurosci. Res., 2008, 86(12), 2705-2721.
[http://dx.doi.org/10.1002/jnr.21722] [PMID: 18500755]
[23]
Hota, K.B.; Hota, S.K.; Chaurasia, O.P.; Singh, S.B. Acetyl-L-carnitine-mediated neuroprotection during hypoxia is attributed to ERK1/2-Nrf2-regulated mitochondrial biosynthesis. Hippocampus, 2012, 22(4), 723-736.
[http://dx.doi.org/10.1002/hipo.20934] [PMID: 21542052]
[24]
White, H.L.; Scates, P.W. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem. Res., 1990, 15(6), 597-601.
[http://dx.doi.org/10.1007/BF00973749] [PMID: 2215852]
[25]
Obeid, R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients, 2013, 5(9), 3481-3495.
[http://dx.doi.org/10.3390/nu5093481] [PMID: 24022817]
[26]
Resstel, L.B.; de Andrade, C.R.; Haddad, R.; Eberlin, M.N.; de Oliveira, A.M.; Corrêa, F.M. Hyperhomocysteinaemia-induced cardiovascular changes in rats. Clin. Exp. Pharmacol. Physiol., 2008, 35(8), 949-956.
[http://dx.doi.org/10.1111/j.1440-1681.2008.04940.x] [PMID: 18430058]
[27]
Celotto, A.C.; Fukada, S.Y.; Laurindo, F.R.; Haddad, R.; Eberlin, M.N.; de Oliveira, A.M. Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries. Amino Acids, 2010, 38(5), 1515-1522.
[http://dx.doi.org/10.1007/s00726-009-0368-y] [PMID: 19876715]
[28]
Jakubowski, H. Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels. J. Biol. Chem., 1997, 272(3), 1935-1942.
[http://dx.doi.org/10.1016/S0021-9258(19)67504-6] [PMID: 8999883]
[29]
Kumar, S.; Ivanov, S.; Lagunin, A.; Goel, R.K. Attenuation of hyperhomocysteinemia induced vascular dementia by sodium orthovanadate perhaps via PTP1B: Pertinent downstream outcomes. Behav. Brain Res., 2019, 364, 29-40.
[http://dx.doi.org/10.1016/j.bbr.2019.01.039] [PMID: 30721761]
[30]
Yu, H.; Zhang, Z.L.; Chen, J.; Pei, A.; Hua, F.; Qian, X.; He, J.; Liu, C.F.; Xu, X. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS One, 2012, 7(3), e33584.
[http://dx.doi.org/10.1371/journal.pone.0033584] [PMID: 22438954]
[31]
Willebrords, J.; Maes, M.; Crespo Yanguas, S.; Vinken, M. Inhibitors of connexin and pannexin channels as potential therapeutics. Pharmacol. Ther., 2017, 180, 144-160.
[http://dx.doi.org/10.1016/j.pharmthera.2017.07.001] [PMID: 28720428]
[32]
Shibata, M.; Yamasaki, N.; Miyakawa, T.; Kalaria, R.N.; Fujita, Y.; Ohtani, R.; Ihara, M.; Takahashi, R.; Tomimoto, H. Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke, 2007, 38(10), 2826-2832.
[http://dx.doi.org/10.1161/STROKEAHA.107.490151] [PMID: 17761909]
[33]
Hattori, Y.; Enmi, J.; Kitamura, A.; Yamamoto, Y.; Saito, S.; Takahashi, Y.; Iguchi, S.; Tsuji, M.; Yamahara, K.; Nagatsuka, K.; Iida, H.; Ihara, M. A novel mouse model of subcortical infarcts with dementia. J. Neurosci., 2015, 35(9), 3915-3928.
[http://dx.doi.org/10.1523/JNEUROSCI.3970-14.2015] [PMID: 25740520]
[34]
Broadbent, N.J.; Gaskin, S.; Squire, L.R.; Clark, R.E. Object recognition memory and the rodent hippocampus. Learn. Mem., 2009, 17(1), 5-11.
[http://dx.doi.org/10.1101/lm.1650110] [PMID: 20028732]
[35]
Kolling, J.; Longoni, A.; Siebert, C.; Dos Santos, T.M.; Marques, E.P.; Carletti, J.; Pereira, L.O.; Wyse, A.T.S. Severe hyperhomocysteinemia decreases creatine kinase activity and causes memory impairment: Neuroprotective role of creatine. Neurotox. Res., 2017, 32(4), 585-593.
[http://dx.doi.org/10.1007/s12640-017-9767-0] [PMID: 28656547]
[36]
Hosseini, N.; Alaei, H.; Reisi, P.; Radahmadi, M. The effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease. Int. J. Prev. Med., 2013, 4(2), 187-192.
[PMID: 23543475]
[37]
Choi, S.J.; Kim, M.J.; Heo, H.J.; Hong, B.; Cho, H.Y.; Kim, Y.J.; Kim, H.K.; Lim, S.T.; Jun, W.J.; Kim, E.K.; Shin, D.H. Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit. Mol. Cells, 2007, 24(1), 113-118.
[PMID: 17846505]
[38]
Itoh, J.; Nabeshima, T.; Kameyama, T. Utility of an elevated plus- maze for the evaluation of memory in mice: Effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology (Berl.), 1990, 101(1), 27-33.
[http://dx.doi.org/10.1007/BF02253713] [PMID: 2343073]
[39]
Dhingra, D.; Parle, M.; Kulkarni, S.K. Memory enhancing activity of Glycyrrhiza glabra in mice. J. Ethnopharmacol., 2004, 91(2-3), 361-365.
[http://dx.doi.org/10.1016/j.jep.2004.01.016] [PMID: 15120462]
[40]
Dhingra, D.; Kumar, V. Memory-enhancing activity of palmatine in mice using elevated plus maze and morris water maze. Adv. Pharmacol. Sci., 2012, 2012, 357368.
[http://dx.doi.org/10.1155/2012/357368] [PMID: 23193393]
[41]
Higaki, A.; Mogi, M.; Iwanami, J.; Min, L.J.; Bai, H.Y.; Shan, B.S.; Kukida, M.; Kan-No, H.; Ikeda, S.; Higaki, J.; Horiuchi, M. Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning. PLoS One, 2018, 13(2), e0191708.
[http://dx.doi.org/10.1371/journal.pone.0191708] [PMID: 29415035]
[42]
Pahwa, P.; Goel, R.K. Antidepressant-like effect of a standardized hydroethanolic extract of Asparagus adscendens in mice. Indian J. Pharmacol., 2019, 51(2), 98-108.
[http://dx.doi.org/10.4103/ijp.IJP_116_17] [PMID: 31142945]
[43]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[44]
Esterbauer, H.; Cheeseman, K.H. Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal. Methods Enzymol., 1990, 186, 407-421.
[http://dx.doi.org/10.1016/0076-6879(90)86134-H] [PMID: 2233308]
[45]
Cadenas, S.; Rojas, C.; Pérez-Campo, R.; López-Torres, M.; Barja, G. Vitamin E protects guinea pig liver from lipid peroxidation without depressing levels of antioxidants. Int. J. Biochem. Cell Biol., 1995, 27(11), 1175-1181.
[http://dx.doi.org/10.1016/1357-2725(95)00077-3] [PMID: 7584603]
[46]
Mehta, M.; Adem, A.; Sabbagh, M. New acetylcholinesterase inhibitors for Alzheimer’s disease. Int. J. Alzheimers Dis., 2012, 2012, 728983.
[http://dx.doi.org/10.1155/2012/728983] [PMID: 22216416]
[47]
Colović, M.B.; Krstić, D.Z.; Lazarević-Pašti, T.D.; Bondžić, A.M.; Vasić, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11(3), 315-335.
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[48]
Seltzer, B. Donepezil: An update. Expert Opin. Pharmacother., 2007, 8(7), 1011-1023.
[http://dx.doi.org/10.1517/14656566.8.7.1011] [PMID: 17472546]
[49]
Farlow, M.; Veloso, F.; Moline, M.; Yardley, J.; Brand-Schieber, E.; Bibbiani, F.; Zou, H.; Hsu, T.; Satlin, A. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer’s disease. BMC Neurol., 2011, 11, 57.
[http://dx.doi.org/10.1186/1471-2377-11-57] [PMID: 21612646]
[50]
Malouf, M.; Grimley, E.J.; Areosa, S.A. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Sys. Rev., 2003, (4), CD004514.
[http://dx.doi.org/10.1002/14651858.CD004514]
[51]
de Koning, E.J.; van der Zwaluw, N.L.; van Wijngaarden, J.P.; Sohl, E.; Brouwer-Brolsma, E.M.; van Marwijk, H.W.; Enneman, A.W.; Swart, K.M.; van Dijk, S.C.; Ham, A.C.; van der Velde, N.; Uitterlinden, A.G.; Penninx, B.W.; Elders, P.J.; Lips, P.; Dhonukshe-Rutten, R.A.; van Schoor, N.M.; de Groot, L.C. Effects of two-year vitamin B12 and folic acid supplementation on depressive symptoms and quality of life in older adults with elevated homocysteine concentrations: Additional results from the B-PROOF study, an RCT. Nutrients, 2016, 8(11), 748.
[http://dx.doi.org/10.3390/nu8110748] [PMID: 27886078]
[52]
Vitamin B12 and cognitive function: An evidence-based analysis. Ont. Health Technol. Assess. Ser., 2013, 13(23), 1-45.
[PMID: 24379897]
[53]
Ford, A.H.; Almeida, O.P. Effect of homocysteine lowering treatment on cognitive function: A systematic review and meta-analysis of randomized controlled trials. J. Alzheimers Dis., 2012, 29(1), 133-149.
[http://dx.doi.org/10.3233/JAD-2012-111739] [PMID: 22232016]
[54]
van der Zwaluw, N.L.; Dhonukshe-Rutten, R.A.; van Wijngaarden, J.P.; Brouwer-Brolsma, E.M.; van de Rest, O.; In 't Veld, P.H. Results of 2-year vitamin B treatment on cognitive performance: Secondary data from an RCT. Neurology, 2014, 83(23), 2158-2166.
[55]
Ozek, C.; Kanoski, S.E.; Zhang, Z.Y.; Grill, H.J.; Bence, K.K. Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. J. Biol. Chem., 2014, 289(46), 31682-31692.
[http://dx.doi.org/10.1074/jbc.M114.603621] [PMID: 25288805]
[56]
Sun, M.; Izumi, H.; Shinoda, Y.; Fukunaga, K. Neuroprotective effects of protein tyrosine phosphatase 1B inhibitor on cerebral ischemia/reperfusion in mice. Brain Res., 2018, 1694, 1-12.
[http://dx.doi.org/10.1016/j.brainres.2018.04.029] [PMID: 29705606]
[57]
Wilasrusmee, C.; Shah, G.; Kittur, S.; Halverson, A.; Bruch, D.; Kittur, D. Signal transduction pathway in endothelial dysfunction. Surg. Infect. (Larchmt.), 2004, 5(1), 9-14.
[http://dx.doi.org/10.1089/109629604773860255] [PMID: 15142418]
[58]
Verma, A.; Sharma, S. Beneficial effect of protein tyrosine phosphatase inhibitor and phytoestrogen in dyslipidemia-induced vascular dementia in ovariectomized rats. J. Stroke Cerebrovasc. Dis., 2015, 24(11), 2434-2446.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.02.019] [PMID: 26324516]
[59]
Ahmed, H.H. Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer’s disease in rat model. Exp. Toxicol. Pathol., 2012, 64(6), 549-556.
[http://dx.doi.org/10.1016/j.etp.2010.11.012] [PMID: 21183322]
[60]
Nestor, P.J.; Fryer, T.D.; Hodges, J.R. Declarative memory impairments in Alzheimer’s disease and semantic dementia. Neuroimage, 2006, 30(3), 1010-1020.
[http://dx.doi.org/10.1016/j.neuroimage.2005.10.008] [PMID: 16300967]
[61]
Machado, S.; Cunha, M.; Minc, D.; Portella, C.E.; Velasques, B.; Basile, L.F.; Cagy, M.; Piedade, R.; Ribeiro, P. Alzheimer’s disease and implicit memory. Arq. Neuropsiquiatr., 2009, 67(2A), 334-342.
[http://dx.doi.org/10.1590/S0004-282X2009000200034] [PMID: 19547837]
[62]
Jahn, H. Memory loss in Alzheimer’s disease. Dialogues Clin. Neurosci., 2013, 15(4), 445-454.
[http://dx.doi.org/10.31887/DCNS.2013.15.4/hjahn] [PMID: 24459411]
[63]
Streck, E.L.; Bavaresco, C.S.; Netto, C.A.; Wyse, A.T. Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task. Behav. Brain Res., 2004, 153(2), 377-381.
[http://dx.doi.org/10.1016/j.bbr.2003.12.013] [PMID: 15265632]
[64]
Chai, G.S.; Jiang, X.; Ni, Z.F.; Ma, Z.W.; Xie, A.J.; Cheng, X.S.; Wang, Q.; Wang, J.Z.; Liu, G.P. Betaine attenuates Alzheimer- like pathological changes and memory deficits induced by homocysteine. J. Neurochem., 2013, 124(3), 388-396.
[http://dx.doi.org/10.1111/jnc.12094] [PMID: 23157378]
[65]
Yang, S.P.; Yang, X.Z.; Cao, G.P. Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Mol. Med. Rep., 2015, 12(1), 1145-1150.
[http://dx.doi.org/10.3892/mmr.2015.3490] [PMID: 25776802]
[66]
Burbaeva, G.Sh.; Savushkina, O.K.; Dmitriev, A.D. Brain isoforms of creatine kinase in health and mental diseases: Alzheimer's disease and schizophrenia. Vestn. Ross. Akad. Med. Nauk, 1999, (1), 20-24.
[PMID: 10078058]
[67]
Pirchl, M.; Ullrich, C.; Humpel, C. Differential effects of short- and long-term hyperhomocysteinaemia on cholinergic neurons, spatial memory and microbleedings in vivo in rats. Eur. J. Neurosci., 2010, 32(9), 1516-1527.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07434.x] [PMID: 21044172]
[68]
Dam, K.; Füchtemeier, M.; Farr, T.D.; Boehm-Sturm, P.; Foddis, M.; Dirnagl, U.; Malysheva, O.; Caudill, M.A.; Jadavji, N.M. Increased homocysteine levels impair reference memory and reduce cortical levels of acetylcholine in a mouse model of vascular cognitive impairment. Behav. Brain Res., 2017, 321, 201-208.
[http://dx.doi.org/10.1016/j.bbr.2016.12.041] [PMID: 28087280]
[69]
Carta, A.; Calvani, M. Acetyl-L-carnitine: A drug able to slow the progress of Alzheimer’s disease? Ann. N.Y. Acad. Sci., 1991, 640, 228-232.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb00223.x] [PMID: 1776743]
[70]
Calvani, M.; Carta, A.; Caruso, G.; Benedetti, N.; Iannuccelli, M. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer’s disease. Ann. N.Y. Acad. Sci., 1992, 663, 483-486.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb38710.x] [PMID: 1482095]
[71]
Traina, G. The neurobiology of acetyl-L-carnitine. Front. Biosci., 2016, 21, 1314-1329.
[http://dx.doi.org/10.2741/4459] [PMID: 27100509]
[72]
Streck, E.L.; Vieira, P.S.; Wannmacher, C.M.; Dutra-Filho, C.S.; Wajner, M.; Wyse, A.T. In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. Metab. Brain Dis., 2003, 18(2), 147-154.
[http://dx.doi.org/10.1023/A:1023815119931] [PMID: 12822833]
[73]
Kim, S.H.; Kim, K.; Ahn, J.H.; Chang, H.K. Increased expression of tumor necrosis factor-alpha in the rat hippocampus after acute homocysteine administration. J. Epilepsy Res., 2011, 1(1), 6-12.
[http://dx.doi.org/10.14581/jer.11002] [PMID: 24649438]

Rights & Permissions Print Cite
Article Metrics
54
1
© 2024 Bentham Science Publishers | Privacy Policy