Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

This study aimed to investigate the effect of KATP channel opening with nicorandil or blockade with glibenclamide on neurodegeneration in mice following systemic rotenone injection. Mice were treated with rotenone (1.5 mg/kg subcutaneously; 3 times/week on days 1, 3, 5) for 3 successive weeks. Starting on the 1st day of rotenone treatment, mice were daily treated intraperitoneally with either nicorandil (6 or 10 mg/kg), glibenclamide (3 or 5 mg/kg) or l-dopa (25 mg/kg). Behavioral examination using the wire hanging and stair tests were performed. Striatal levels of dopamine, tyrosine-hydroxylase, caspases (3, 8, 9), Bcl-2, and tumor necrosis factor-Ü (TNF-Ü) were determined. Rotenone injection resulted in a decrease in motor strength and activity in mice. In addition, striatal apoptosis was evidenced by decreased level of the antiapoptotic protein Bcl-2, the increase in the apoptotic markers caspase 3, 8 and 9 as well as by histopathological alterations. Treatment with glibenclamide and l-dopa exerted a neuroprotective effect as revealed by the increase of Bcl2, tyrosine-hydroxylase and dopamine while decreasing caspase 3, 8, 9 and TNF- Ü immunoreactivity. On the other hand, nicorandil administration didn{u2019}t ameliorate rotenone-induced striatal neurodegeneration. These data suggest an antiapoptotic and anti-inflammatory action for glibenclamide and l-dopa in the rotenone model of Parkinson{u2019}s disease in mice

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