interaction of memantine with homocysteine on the apoptosis in the rat hippocampus cells

it has been hypothesized that elevated plasma homocysteine (hcy) plays a role in the pathogenesis of alzheimer’s disease (ad) and age-related cognitive decline. the mechanism of hcy neurotoxicity in the brain is controversial as well hcy is a ligand of nmda receptor. memantine, an uncompetitive antagonist of n-methyl-d-aspartate (nmda) receptors approved for the treatment of moderate to severe alzheimer's disease. hcy was injected 0.5 μmol/μl in the hippocampus of the rat brain and memantine hydrochloride was injected 10mg/kg intraperitoneally 1 hour prior to hcy injection. after five days, rats were killed and whole brain were taken out, fixed, and embedded in paraffin. the slices of the rat brain were prepared and immunohistochemical analysis was done to reveal the protein expression of bax, bcl-2, and the activation of caspase 3 in the rat hippocampus layers. results showed significant increase of bax and caspase-3 immunoreactivity in hippocampus of rat brain in hcy group. also an increase in bax/bcl-2 ratio in rat hippocampus cells .memantine pretreatment could not change the levels of bax, bcl-2, caspase-3 significantly in rat’s hippocampus cells. these findings suggest that memantine could not antagonize hcy – induced apoptosis. hcy may induce apoptosis via the other oxidative stress mechanism in the rat brain. potential. it may therefore be interesting that he barberry fruit extracts has the unique capacity to quench free radicals.