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Regulation of tyrosine hydroxylase expression intottering mouse Purkinje cells

Neurotoxicity Research volume 5, pages 521–528 (2003)Cite this article

Abstract

Tottering (tg) mice inherit a missense mutation in the α1A subunit of P/Q-type calcium channels. This mutation results in an increased density of L-type calcium channels in the cerebellum and abnormal regulation of tyrosine hydroxylase (TH) gene expression in a subset of cerebellar Purkinje cells, a cell type that does not normally express TH. The behavioral phenotype includes attacks of dyskinesia, which can be blocked by L-type calcium channel antagonists. To test the hypothesis that cerebellar TH mRNA expression can be manipulatedin vivo by L-type calcium channel blockade, control and tottering mice were chronically treated with the L-type calcium channel antagonist nimodipine. Chronic nimodipine treatment significantly reduced the expression of TH mRNA in tottering mouse Purkinje cells. This effect was observed without altering the increased density of L-type calcium channels in tottering mouse cerebella. Chronic nimodipine treatment had no effect on TH mRNA expression in tottering mouse catecholaminergic neurons, including those of the locus coeruleus and substantia nigra. However, a small reduction in TH mRNA expression in the substantia nigra of control mice was observed after drug treatment. These data suggest that the abnormal expression of TH in tottering mouse Purkinje cells is regulated by Purkinje cell excitability.

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Author notes

  1. Brandy E. Fureman

    Present address: Office of Science Policy and Planning, National Institute of Neurological Disorders and Stroke, 20892, Bethesda, MD, USA

  2. Daniel B. Campbell

    Present address: John F. Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University, 37232, Nashville, TN, USA

Affiliations

  1. Department of Neurology, Johns Hopkins University, 21152, Baltimore, MD, USA

    Brandy E. Fureman, Daniel B. Campbell & Ellen J. Hess

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  1. Brandy E. Fureman
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  2. Daniel B. Campbell
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  3. Ellen J. Hess
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Correspondence to Ellen J. Hess.

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Fureman, B.E., Campbell, D.B. & Hess, E.J. Regulation of tyrosine hydroxylase expression intottering mouse Purkinje cells. neurotox res 5, 521–528 (2003). https://doi.org/10.1007/BF03033162

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  • DOI: https://doi.org/10.1007/BF03033162

Keywords

  • Tottering
  • Gene expression
  • Dihydropyridine
  • Cerebellum
  • Mouse mutant calcium channel
  • Nimodipine