Central noradrenaline metabolism in cerebellar ataxic mice

Central noradrenaline (NA) metabolism was investigated in 4 types of ataxic mutant mice, weaver, reeler, staggerer and rolling mouse Nagoya (RMN) and hypocerebellar mice experimentally produced by neonatal treatment with cytosine arabinoside (ara-C). As neurochemical markers for synthesis, steady-state level and turnover of NA, we measured tyrosine hydroxylase (TH) activity, NA and total (free + conjugated) 3-methoxy-4-hydroxyphenylethyleneglycol (total MHPG) concentrations in the cerebellum, cerebral cortex and spinal cord. In the weaver and staggerer whose cerebellar weight loss was severe (40 and 21% of controls, respectively), the 3 neurochemical markers were all increased in the cerebellum, and a similar increase was observed in other regions. In the reeler, the 3 markers were also markedly increased in the cerebellum, but no similar pattern of increase was observed in other regions. In the RMN whose cerebellum showed the least weight loss (76% of control), only TH activity and MHPG concentration were increased in the cerebellum and spinal cord but not in the cerebral cortex. In ara-C-treated mice, the neurochemical markers were also increased in the cerebellum, but to a lesser extent in other regions. These results suggest that, although total contents and total activity of these markers per whole cerebellum were significantly decreased, the central NA metabolism was basically enhanced throughout the CNS of the cerebellar ataxic mice irrespective of their cause. The degree and extent of this enhancement appeared to be correlated with the degree of the cerebellar weight loss.