Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington's disease

Dénes Zádori, Andrea Geisz, Eniko Vámos, László Vécsei, Péter Klivényi

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Huntington's disease (HD) is one of the chronic devastating neurodegenerative disorders. The pathophysiological processes clearly involve both excitotoxicity and reduced gene transcription due to the decreased level of histone acetylation, accompanied by the loss of γ-aminobutyric acidergic (GABAergic) medium-sized spiny neurons in the striatum as a pathological hallmark of HD. Thus, the antiepileptic drug valproate, which has proved GABAergic, antiexcitotoxic and histone deacetylase inhibitor effects, might be of value by exerting a beneficial neuroprotective effect. We have now tested this drug in the N171-82Q transgenic mouse model of HD, following its chronic intraperitoneal administration in a daily dose of 100 mg/kg. Valproate significantly prolonged the survival of the transgenic mice and significantly ameliorated their diminished spontaneous locomotor activity, without exerting any noteworthy side-effect on their behaviour or the striatal dopamine content at the dose administered. The beneficial effect of valproate is probably explained by its complex pharmacological activity. As several previous clinical trials carried out with valproate did not indicate any positive effect in HD, it is worth considering the design of new studies based on a well-planned treatment regime with higher dose, using valproate in monotherapy or in combination therapy with a high number of participating patients.

Original languageEnglish
Pages (from-to)148-153
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume94
Issue number1
DOIs
Publication statusPublished - Nov 1 2009

Keywords

  • Huntington's disease
  • N171-82Q
  • Transgenic mice
  • Valproate

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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