Effect of zonisamide co-administration with levodopa on global gene expression in the striata of rats with Parkinson’s disease

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.

► Long-term use of levodopa has been reported to have adverse effects.
► Zonisamide (ZNS) has beneficial effects for patients with Parkinson’s disease (PD).
► We aimed to elucidate the mechanism underlying ZNS’s protective effects against PD.
► Our results indicated neuroprotective effects of ZNS co-administered with levodopa.