INCREASED ACTIVITY OF TYROSINE-HYDROXYLASE IN THE CEREBELLUM OF THE X-IRRADIATED DYSTONIC RAT

The exposure of the cephalic end of rats to repeated doses of X-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 +/- 4 ng/CE and 2.8 +/- 1.5 ng/CE, respectively) and X-irradiated rats (17.1 +/- 1 ng/CE and 8.3 +/- 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally X-irradiated animals when compared to age-matched controls (16.4 +/- 1.4 vs 6.32 +/- 0.6 nmol CO2/h/mg prot., p < 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 +/- 23.8 vs 408.2 +/- 21.5 nmol CO2/h/CE, p < 0.01 (controls and X-treated, respectively). These results suggest that X-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.