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

Biochem Biophys Res Commun. 2012 Nov 23;428(3):401-4. doi: 10.1016/j.bbrc.2012.10.067. Epub 2012 Oct 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage*
  • Antiparkinson Agents / administration & dosage*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Gene Expression / drug effects*
  • Gene Expression Profiling
  • Isoxazoles / administration & dosage*
  • Levodopa / administration & dosage*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Oxidopamine / pharmacology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / genetics
  • Parkinson Disease, Secondary / pathology
  • Rats
  • Rats, Wistar
  • Zonisamide

Substances

  • Anticonvulsants
  • Antiparkinson Agents
  • Isoxazoles
  • Zonisamide
  • Levodopa
  • Oxidopamine