Neonatal 6-hydroxydopamine treatment affects GABAA receptor subunit expression during postnatal development of the rat cerebellum

Neurotoxic elimination of noradrenergic terminals by 6-hydroxydopamine (6-OHDA) leads to alteration of the granule cell layer formation. We have studied the developmental expression of GABAA receptor subunits in rat cerebellum after neonatal administration of 6-OHDA during the first postnatal month of life. 6-OHDA was injected subcutaneously. The expression of GABAA receptor subunits was studied by in situ hybridization and immunohistochemistry. The alterations were observed in the neocerebellum - the part of the cerebellum which starts development postnatally. The migration of granule cells was delayed, and the total area of the granule cell layer in the neocerebellum from 6-OHDA-treated rats was reduced to 22.6 +/- 5% of the corresponding area from control rats. In situ hybridization with subunit-specific antisense oligonucleotide probes was performed for alpha 1 alpha 2, alpha 3, alpha 5, alpha 6, beta 1, beta 2, gamma 1 and gamma 2 subunits of the GABA(A) receptor. In neocerebellum, 6-OHDA treatment caused a significant reduction in the alpha 1. alpha 6 and gamma 2 subunit mRNA levels. The expression of the other subunits was not changed. It has been shown that in the postnatal cerebellum alpha 1 and alpha 6 subunits can be detected in granule cells only when the cells had migrated to their final destination. Out findings indicate that a noradrenergic influence may be necessary for the normal maturation and migration of cerebellar granule cells. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.