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-methylD-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.