Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine.
J Neurochem. 2012 Nov 15. Epub 2012 Nov 15. PMID: 23157378
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China.
Hyperhomocysteinemia (Hhcy) may induce memory deficits withβ-amyloid (Aβ) accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and vitamin B12 partially restored the plasma homocysteine level and attenuated tau hyperphosphorylation, Aβ accumulation and memory impairments induced by Hhcy. However, folate and vitamin B12 treatment have no effects on Hhcy which has the methylenetetrahydrofolate reductase genotype mutation. In the present study, we investigated the effects of simultaneous supplement of betaine on Alzheimer-like pathological changes and memory deficits in hyperhomocysteinemic rats after a 2-week induction by venacaudalis injection of homocysteine (Hcy). We found that supplementation of betaine could ameliorate the Hcy-induced memory deficits, enhance LTP and increase dendritic branches numbers and the density of the dendritic spines, with upregulation of NR1, NR2A, synaptotagmin, synaptophysin and phosphorylated synapsin I protein levels. Supplementation of betaine also attenuated the Hcy-induced tau hyperphosphorylation at multiple AD-related sites through activation PP2A with decreased inhibitory demethylated PP2A(C) at Leu309 and phosphorylated PP2A(C) at Tyr307. In addition, supplementation of betaine also decreased Aβ production with decreased presenilin-1 protein levels. Our data suggest that betaine could be a promising candidate for arresting Hcy-induced AD-like pathological changes and memory deficits. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12094.