The spastic Han-Wistar rat

A genetic model of amino acid-induced excitotoxicity

M. S. Levine, R. W. Cohen, Taihung Duong, R. S. Fisher, J. B. Watson, A. T. Campagnoni, J. E. Margulies, N. A. Buchwald

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis. Homozygous animals progressively develop tremor, ataxia and hind limb rigidity beginning 3-4 weeks postnatally. Death ensues at about 10 weeks when animals lose motor control and can no longer feed. Because of the similarities of some of these behavioral symptoms with those induced by cerebellar and brainstem dysfunction, the morphology and physiology of the cerebellum in mutant rats were investigated. Cerebellar Purkinje cells degenerate and asymmetrical disarrangement of the granule cell layer occurs in mutants. The cytoskeleton of Purkinje cells was examined in the mutants by immunohistochemically staining for neurofilament proteins. Alterations in the distribution and arrangement of neurofilament proteins in Purkinje cell perikarya and dendrites and abnormal swellings in axons were found. Functionally, a combined molecular and neurophysiological approach was used in which Xenopus laevis oocytes were injected with mRNA from mutant brains and the ability of the oocytes to express excitatory amino acid receptors was assessed. Oocytes injected with cerebellar mRNA from mutants displayed increased responses to glutamate and kainate. The increased response to excitatory amino acids agonists could represent upregulation of receptors which may be capable of inducing the degeneration of the Purkinje cells. These results suggest that this mutant might be a developmental model of glutamate/kainate neurotoxicity.

Original languageEnglish (US)
Pages (from-to)106-120
Number of pages15
JournalBrain Dysfunction
Volume5
Issue number1-2
StatePublished - 1992
Externally publishedYes

Fingerprint

Muscle Spasticity
Purkinje Cells
Genetic Models
Wistar Rats
Oocytes
Neurofilament Proteins
Amino Acids
Kainic Acid
Glutamic Acid
Excitatory Amino Acid Agonists
Recessive Genes
Cerebellar Diseases
Behavioral Symptoms
Messenger RNA
Aptitude
Xenopus laevis
Glutamate Receptors
Tremor
Paresis
Ataxia

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Levine, M. S., Cohen, R. W., Duong, T., Fisher, R. S., Watson, J. B., Campagnoni, A. T., ... Buchwald, N. A. (1992). The spastic Han-Wistar rat: A genetic model of amino acid-induced excitotoxicity. Brain Dysfunction, 5(1-2), 106-120.

The spastic Han-Wistar rat : A genetic model of amino acid-induced excitotoxicity. / Levine, M. S.; Cohen, R. W.; Duong, Taihung; Fisher, R. S.; Watson, J. B.; Campagnoni, A. T.; Margulies, J. E.; Buchwald, N. A.

In: Brain Dysfunction, Vol. 5, No. 1-2, 1992, p. 106-120.

Research output: Contribution to journalArticle

Levine, MS, Cohen, RW, Duong, T, Fisher, RS, Watson, JB, Campagnoni, AT, Margulies, JE & Buchwald, NA 1992, 'The spastic Han-Wistar rat: A genetic model of amino acid-induced excitotoxicity', Brain Dysfunction, vol. 5, no. 1-2, pp. 106-120.
Levine MS, Cohen RW, Duong T, Fisher RS, Watson JB, Campagnoni AT et al. The spastic Han-Wistar rat: A genetic model of amino acid-induced excitotoxicity. Brain Dysfunction. 1992;5(1-2):106-120.
Levine, M. S. ; Cohen, R. W. ; Duong, Taihung ; Fisher, R. S. ; Watson, J. B. ; Campagnoni, A. T. ; Margulies, J. E. ; Buchwald, N. A. / The spastic Han-Wistar rat : A genetic model of amino acid-induced excitotoxicity. In: Brain Dysfunction. 1992 ; Vol. 5, No. 1-2. pp. 106-120.
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