BioProject

The anti-epileptic drug zonisamide is reported to exert beneficial effects in patients with Parkinson's disease. More...

The anti-epileptic drug zonisamide is reported to exert beneficial effects in patients with Parkinson's disease. To elucidate the pathophysiological mechanisms underlying the anti-parkinsonism effects of zonisamide, we examined the effect of zonisamide co-administered with levodopa in the striata of rats with 6-hydoroxydopamine hemiparkinsonism by using a DNA microarray for genome-wide gene expression profiling. We found that the expression of some genes related to metabolism and nervous system development and function were upregulated by zonisamide; expression of these genes was downregulated by levodopa. Furthermore, many genes related to the immune system and inflammation were downregulated by zonisamide, and their expression was upregulated by levodopa. These results indicate that zonisamide has a protective effect when co-administered with levodopa. Overall design: Rats were anesthetized with pentobarbital 240 mg/kg, i.p. and unilateral lesions of the left medial forebrain bundle were made via injection of 8 mg 6-OHDA hydrobromide in 4 ml of sterile saline containing 0.01% ascorbic acid. Motor disturbance was assessed by counting the number of full rotations per min in a cylindrical container of φ30 cm diameter at 10-min intervals for the first 60 min after METH (3 mg/kg, i.p.) administration [3]. Behavioral screening was carried out after 2-3 weeks of recovery and animals that performed at least 7 turns/min during METH challenge were certified as hemiparkinsonism rats and included in the study. Seven days after METH challenge, hemiparkinsonism rats were treated with saline, L-DOPA (100 mg/kg, i.p.), or L-DOPA (100 mg/kg, i.p.) and ZNS (50 mg/kg, i.p.) once per day for 7 days. L-DOPA was injected 30 min after benserazide hydrochloride (a peripheral decarboxylase inhibitor). ZNS was injected 30 min after L-DOPA injection. The 4 experimental groups were classified as follows: the non-lesioned side of saline-treated 6-OHDA-injected rats (NL), the lesioned side of saline-treated 6-OHDA-injected rats (SL), the lesioned side of L-DOPA-treated 6-OHDA-injected rats (DL), and the lesioned side of L-DOPA and ZNS-treated 6-OHDA-injected rats (ZDL). Three animals were assigned to each group. Less...