Effect And Mechanism Of Homocysteine Endangering On Parkinson's Disease Induced By 6-OHDA

PartⅠ: Effect of homocysteine endangering on Parkinson's disease induced by 6-OHDAObjective: To study the effects of homocysteine endangering on Parkinson's disease induced by 6-hydroxy dopamine (6-OHDA) in Vivo.Methods: 105 rats were divided to 4 groups. 6-OHDA focally administrated to induce PD, 2-h later Hcy or 0.9%Nacl was administrated in the ipsolateral substantia nigra. Immolunohistochemical technique was used to detect the injury of substantia ngral during the development of rat PD model on day l, 7 and 14 after injection.Results: The number of stantia nigral apoptosis induced by 6-OHDA showed significantly increasing after treatment with Hcy compared with the controls (P<0.01). And the number of TH-stained neurons was decreased and dendrites were fragmented and truncated.Conclusions: Focal infusion of Hcy into the substantia nigra increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration and apoptosis. PartⅡ: Effect of NF-κB on substaintia nigra neurons injury induced by homocysteineObjective: To study effect of nuclear factorκappa B (NF-κB) on substaintia nigra neurons injury induced by homocysteine in Vivo.Methods: 105 rats were divided to 3 groups. With or without a specific inhibitor of NF-κB, PDTC applied, 6-OHDA focally administrated to induce PD, 2-h later Hcy or 0.9%Nacl were administrated in the ipsolateral substantia nigra. Immolunohisto -chemical technique was used to observe the number of TH-stained neurons, nigra apoptosis and the changes of the expression of NF-κB on the hour4,day l,2, 7 and 14 after injection.Results: After treatment with Hcy, the numbers of of TH-stained neurons induced by 6-OHDA was decreased. And the number of nigral apoptosis induced by 6-OHDA was increased, so was the expression of NF-κB. PDTC significantly inhibited NF-κB activating ,decreased the number of nigral apoptosis ,and increase the number of TH-stained neurons .Conclusions: Focal infusion of Hcy into the substantia nigra increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration and apoptosis, the activation of NF-κB may be a crucial mechanism ; PDTC attenuated the injury induced by Hcy and 6-OHDA.