Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease

E. Vámos, Krisztina Voros, Denes Zadori, L. Vécsei, P. Klivényi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Huntington's disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters. In this study, we examined the effects of probenecid on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. After probenecid administration, the duration of survival improved by 35%. The motor activity was significantly ameliorated as compared with the control transgenic group. Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that probenecid may exert a neuroprotective effect by increasing the membrane transport of protective compounds, and/or inhibiting the toxic compounds.

Original languageEnglish
Pages (from-to)1079-1086
Number of pages8
JournalJournal of Neural Transmission
Volume116
Issue number9
DOIs
Publication statusPublished - Sep 2009

Fingerprint

Probenecid
Genetically Modified Animals
Huntington Disease
Neuroprotective Agents
Animal Models
Organic Anion Transporters
Multidrug Resistance-Associated Proteins
Membranes
Poisons
Transgenic Mice
Motor Activity
Control Groups

Keywords

  • Huntington's disease
  • Kynurenic acid
  • Neuroprotection
  • Probenecid

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease. / Vámos, E.; Voros, Krisztina; Zadori, Denes; Vécsei, L.; Klivényi, P.

In: Journal of Neural Transmission, Vol. 116, No. 9, 09.2009, p. 1079-1086.

Research output: Contribution to journalArticle

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