Dt Mutant Research Articles

Alterations in the noradrenergic projection to the cerebellum of the dystonic ( dt) rat

The genetically dystonic rat ( dt) has elevated resting levels of cerebellar norepinephrine (NE) in comparison with phenotypically normal littermates. This difference is not secondary to cerebellar hypoplasia. Increased NE is observed as early as postnatal day 12, when clinical symptoms have become evident. The elevation in cerebellar NE levels in the dt rat involves all cerebellar areas, but is not generalized to all terminal fields of the locus coeruleus. Elevations in cerebellar NE are followed developmentally by a reduction in sensitivity to the NE-depleting effects of reserpine, a change which is also confined to the cerebellum. The effects of amphetamine and the tyrosine hydroxylase inhibitor alpha-methyl- para-tyrosine were similar in normal and dt rats. Levels of the major cerebellar metabolite of NE, 3-methoxy-4-hydroxyphenylglycol, did not differ between mutant and normal animals. Nor were any changes noted in the number or affinity of beta-adrenergic receptors. These data indicate that there is a regional alteration in NE storage. Cerebellar morphology appears normal in the dt rat, except for a decrease in Purkinje cell size. This change and other evidence of biochemical abnormalities in the Purkinje cells suggest that the alterations in cerebellar NE in the dt mutant may be a secondary response to a functional change in the target neuron for this system, the Purkinje cell.