Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat

Randy W. Cohen, Robin S. Fisher, Taihung Duong, Vance W. Handley, Anthony T. Campagnoni, Chester D. Hull, Nathaniel A. Buchwald, Michael S. Levine

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM l-glutamate, 500 μM kainate, 500 μM quisqualate, 200 μM N-methyl-d-aspartate (NMDA) or 1 mM γ-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalMolecular Brain Research
Volume11
Issue number1
DOIs
StatePublished - Aug 1991

Fingerprint

Excitatory Amino Acids
Muscle Spasticity
Cerebellum
Kainic Acid
Oocytes
Wistar Rats
Glutamic Acid
Quisqualic Acid
Messenger RNA
Brain
Aspartic Acid
Aminobutyrates
Recessive Genes
Kainic Acid Receptors
Cerebellar Cortex
Purkinje Cells
Glutamate Receptors
Tremor
Paresis
Ataxia

Keywords

  • Cerebellum
  • Glutamate
  • Granule cell
  • Han-Wistar rat
  • Kainate
  • Purkinje cell
  • Xenopus oocyte
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Cohen, R. W., Fisher, R. S., Duong, T., Handley, V. W., Campagnoni, A. T., Hull, C. D., ... Levine, M. S. (1991). Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat. Molecular Brain Research, 11(1), 27-36. https://doi.org/10.1016/0169-328X(91)90017-R

Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat. / Cohen, Randy W.; Fisher, Robin S.; Duong, Taihung; Handley, Vance W.; Campagnoni, Anthony T.; Hull, Chester D.; Buchwald, Nathaniel A.; Levine, Michael S.

In: Molecular Brain Research, Vol. 11, No. 1, 08.1991, p. 27-36.

Research output: Contribution to journalArticle

Cohen, RW, Fisher, RS, Duong, T, Handley, VW, Campagnoni, AT, Hull, CD, Buchwald, NA & Levine, MS 1991, 'Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat', Molecular Brain Research, vol. 11, no. 1, pp. 27-36. https://doi.org/10.1016/0169-328X(91)90017-R
Cohen, Randy W. ; Fisher, Robin S. ; Duong, Taihung ; Handley, Vance W. ; Campagnoni, Anthony T. ; Hull, Chester D. ; Buchwald, Nathaniel A. ; Levine, Michael S. / Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat. In: Molecular Brain Research. 1991 ; Vol. 11, No. 1. pp. 27-36.
@article{70ff039ab2694c438718b840b0205172,
title = "Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat",
abstract = "A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM l-glutamate, 500 μM kainate, 500 μM quisqualate, 200 μM N-methyl-d-aspartate (NMDA) or 1 mM γ-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.",
keywords = "Cerebellum, Glutamate, Granule cell, Han-Wistar rat, Kainate, Purkinje cell, Xenopus oocyte, mRNA",
author = "Cohen, {Randy W.} and Fisher, {Robin S.} and Taihung Duong and Handley, {Vance W.} and Campagnoni, {Anthony T.} and Hull, {Chester D.} and Buchwald, {Nathaniel A.} and Levine, {Michael S.}",
year = "1991",
month = "8",
doi = "10.1016/0169-328X(91)90017-R",
language = "English (US)",
volume = "11",
pages = "27--36",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat

AU - Cohen, Randy W.

AU - Fisher, Robin S.

AU - Duong, Taihung

AU - Handley, Vance W.

AU - Campagnoni, Anthony T.

AU - Hull, Chester D.

AU - Buchwald, Nathaniel A.

AU - Levine, Michael S.

PY - 1991/8

Y1 - 1991/8

N2 - A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM l-glutamate, 500 μM kainate, 500 μM quisqualate, 200 μM N-methyl-d-aspartate (NMDA) or 1 mM γ-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.

AB - A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM l-glutamate, 500 μM kainate, 500 μM quisqualate, 200 μM N-methyl-d-aspartate (NMDA) or 1 mM γ-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.

KW - Cerebellum

KW - Glutamate

KW - Granule cell

KW - Han-Wistar rat

KW - Kainate

KW - Purkinje cell

KW - Xenopus oocyte

KW - mRNA

UR - http://www.scopus.com/inward/record.url?scp=0025901110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025901110&partnerID=8YFLogxK

U2 - 10.1016/0169-328X(91)90017-R

DO - 10.1016/0169-328X(91)90017-R

M3 - Article

C2 - 1685005

AN - SCOPUS:0025901110

VL - 11

SP - 27

EP - 36

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -