Altered neuronal nitric oxide synthase expression in the cerebellum of calcium channel mutant mice

Im Joo Rhyu, Sang Soep Nahm, Seung Jun Hwang, Hyun Kim, Young Suk Suh, Sen Ich Oda, Tamy C. Frank, Louise C. Abbott

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Tottering, rolling Nagoya, and leaner mutant mice all exhibit cerebellar ataxia to varying degrees, from mild (tottering mice) to severe (leaner mice). Collectively, these mice are regarded as tottering locus mutants because each of these mutant mice expresses a different autosomal recessive mutation in the gene coding for the α1A calcium ion channel protein, which is the pore forming subunit for P/Q-type high voltage activated calcium ion channels. These mutant mice all exhibit varying degrees of cerebellar dysfunction and neuronal cell death. Nitric oxide (NO) is an important messenger molecule in the central nervous system, especially in the cerebellum, and it is produced via the enzyme, nitric oxide synthase (NOS). We investigated expression of neuronal-NOS (n-NOS) in the cerebella of all three mutant mice, as revealed by NADPH-diaphorase (NADPH-d) histochemical staining, quantitation of n-NOS protein using Western blotting and quantitation of n-NOS mRNA using in situ hybridization. The expression of n-NOS mRNA and protein as well as the NADPH-d histochemical reaction were elevated in tottering and rolling Nagoya cerebella. n-NOS mRNA and the NADPH-d histochemical reaction were decreased in the leaner cerebellum, but the leaner mouse n-NOS protein concentration was not significantly different compared to age- and gender-matched controls. These findings suggest that NO may act as an important mediator in the production of the neuropathology observed in these mutant mice.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalBrain Research
Volume977
Issue number2
DOIs
Publication statusPublished - 2003 Jul 11

Keywords

  • Ataxia
  • Epilepsy
  • In situ hybridization histochemistry
  • NADPH-d
  • Nitric oxide
  • P/Q-type calcium channels

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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