Betaine Attenuates Alzheimer-like Pathological Changes And Memory Deficits Induced By Homocysteine

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases,with the characteristic pathological changes: neurofibrillary tangles (NFT) and senileplaques (SP). Hyperhomocystinemia (Hhcy) may induce tau hyperphosphorylationand β-amyloid (Aβ) accumulation, and cause Alzheimer’s disease. Simultaneoussupplement of folate and vitamin B12partially reduce the plasma homocysteine level,attenuated tau hyperphosphorylation, decrease Aβ accumulation and restored memoryimpairments induced by Hhcy. In some populations with methylenetetrahydrofolatereductase (MTHFR) genotype mutations, however, simultaneous supplement of folateand vitamin B12has no effects on Hhcy. Betaine metabolizes Hcy through providinga methyl group with the help of betaine-homocysteine methyl transferase (BHMT).But it’s not clear whether betaine attenuates Alzheimer-like pathological changes andmemory deficits induced by homocysteine. Methods: We injected the rats by venacaudalis with homocysteine (Hcy) for2-week to make the rats hyperhomocysteinemic,and researched the reverse effect of betaine with a simultaneous supplement ofbetaine. We detected the rat’s learning and memory ability, changes of dendrite,levels of tau phosphorylation and memory related protein, and Aβ accumulation,separately by morris water maze test, golgi stain, western blotting,immunohistochemistry, and elisa. Results: We found that simultaneous supplementof betaine could reverse the effection of Hhcy, ameliorate memory deficits, enhanceLTP, increase dendritic branches numbers and the density of the dendritic spines,improve levels of NR1, NR2A, synaptotagmin, Synaptophysin and phosphorylatedsynapsin I. Betaine could downregulate tau hyperphosphorylation at multipleAD-related sites through activation PP2ACwith decreased demethylation at Leu309and phosphorylation at Tyr307. Betaine could also decrease Aβ production byreducing level of PS-1. Conclusion: These datas indicate that betaine could reverseHcy-induced AD-like pathological changes and memory deficits.