Homocysteine intracerebroventricular injection induces apoptosis in the Substantia Nigra cells and Parkinson like behavior in rat

Introduction: Parkinson Disease is a degenerative disorder of the central nervous system. The motor symptoms of Parkinson s disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of this cell death is unknown. Homocysteine (Hcy) is a non-protein amino acid. It is a homologue of the amino acid Cysteine. Elevated levels of homocysteine in plasma have been associated with a number of disease states.Methods: Hcy (2 μmol / μl) was injected intracerebroventricular (i.c.v) in rat, five days later, locomotor activity was measured with open field apparatus, and Also apoptosis was investigated in Substantia Nigra cells by immunohistochemical (IHC) analysis Bax and Bcl2 were measured with IHC.Results: Hcy could decrease locomotor activities significantly in rats as well as it could induce apoptosis in Substantia Nigra cells. These results suggest that Hcy is a neurotoxic metabolite and may induce cell death in some nuclei in the brain. Histopathological results revealed that 5 days after Hcy (i.c.v.). Injection, Bax level was significantly increased while Bcl-2 level was dramatically decreased in the Substantia Nigra in comparison to the vehicle and control groupsDiscussion: The results of the present study showed that Hcy was neurotoxic for rats. It has been reported that hyper homocysteinemia causes increases in proapoptotic Bax levels and decreases in anti-apoptotic Bcl-2 levels in the rat brain our results suggested that Hcy may induce apoptosis and cell death in rat brain. Hcy may induce oxidative stress and produce ROS that attack all biological macromolecules (e.g. proteins, DNA and lipids). It is suggested that Hcy may be a risk factor for AD and PD.