Neurochemical and histological analysis of motor dysfunction observed in rats with methylnitrosourea-induced experimental cerebellar hypoplasia

Kannosuke Fujimori, Kazuhide Inoue, Ken Nakazawa, Akihiko Maekawa, Makoto Shibutani, Akira Takanaka

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4 Citations (Scopus)

Abstract

Histological and neurochemical changes related to motor dysfunction observed in rats after neonatal treatment with nitrosoureas were examined. Neonatal rats received subcutaneous injections of methylnitrosourea (MNU: 0.125 mmol/kg, s.c.) or ethylnitrosourea (ENU: 0.25 mmol/kg, s.c.) daily at 4,5,6 and 7 days post partum, a period of cerebellar granule cell, stellate cell and basket cell formation. At 14 days and 45 days after birth, MNU-treated rats displayed a lowering in motor coordination skills measured by tests of retainment ability on a rod of 26 mm diameter, chinningclimbing ability on parallel rods or retainment ability on a rotating rod. Histological examination at 14 days after birth showed a cerebellar hypoplasia with reduced cellularity of the internal granule cell layer and a disperse disposition of Purkinje cells in the granule cell layer. Cerebellar growth and cerebellar content and concentration of DNA were remarkably reduced in the MNU-treated rat. The degree of the reduction in cerebellar content of glutamic acid paralleled the degree of the cerebellar hypoplasia at 14 and 45 days after birth. In contrast, the concentrations of gamma-aminobutyric acid, acetylcholine, 5-hydroxytryptamine and norepinephrine were significantly increased by MNU treatment. ENU treatment control did not exert any significant changes in the neurotransmitters and motor coordination. These results suggest that the motor dysfunctions observed in MNU treated rats are induced by unbalanced output activities from Purkinje cells to motor neurons.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalNeurochemical Research
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry

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