MESSENGER-RNAS ENCODING GLUTAMATE-DECARBOXYLASES ARE DIFFERENTIALLY AFFECTED BY NIGROSTRIATAL LESIONS IN SUBPOPULATIONS OF STRIATAL NEURONS

Dopaminergic nigrostriatal neurons constitute one of the major inputs to the striatum, and play a role in the regulation of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme, in striatal neurons. The effect of nigrostriatal lesions on the level of expression of messenger RNAs encoding two distinct isoforms of glutamate decarboxylase was examined at the single cell level with in situ hybridization histochemistry. Rats received a unilateral injection of the neurotoxin 6-hydroxydopamine in the substantia nigra and were sacrificed 2 or 3 weeks later. Sections of the striatum were processed for in situ hybridization histochemistry with radiolabeled RNA probes selective for mRNAs encoding glutamate decarboxylase with molecular weights of 65,000 and 67,000, respectively. In addition, immunohistochemistry with a monospecific antibody for the latter glutamate decarboxylase isoform was performed. In agreement with previous reports, we observed increased labeling for the messenger RNA encoding glutamate decarboxylase (M(r) 67,000) in a population of medium-sized striatal efferent neurons normally expressing low levels of this messenger RNA. We now show that this effect occurred in two striatal compartments, the striosomes and the extrastriosomal matrix, and was accompanied by increased immunostaining for the corresponding protein with a monospecific antibody. In contrast, labeling for messenger RNA encoding GAD (M(r) 67,000) was decreased in a population of medium-sized neurons normally expressing high levels of this messenger RNA and corresponding to GABAergic interneurons. Labeling for messenger RNA encoding glutamate decarboxylase (M(r) 65,000) was not modified in the dopamine-depleted striatum. The results show that dopamine depletion differentially affects gene expression for different isoforms of glutamate decarboxylase in distinct subpopulations of striatal neurons in rat.