Up-regulation of secretoneurin immunoreactivity and secretogranin II mRNA in rat striatum following 6-hydroxydopamine lesioning and chronic L-dopa treatment

Destruction of the nigro-striatal pathway in Parkinson's disease and treatm ent with L-DOPA lead to persistent alterations in basal ganglia output path ways that are poorly characterised. Differential display mRNA analysis was used to study the effects of 6-hydroxydopamine-induced lesions of the media l forebrain bundle on gene expression in the rat striatum. One up-regulated cDNA identified in two independent groups of 6-hydroxydopamine-lesioned an imals was cloned and sequence analysis showed 97% homology to secretogranin IT. Differential up-regulation of secretogranin IT following 6-hydroxydopa mine lesioning was confirmed in a further group of 6-hydroxydopamine-lesion ed rats using TaqMan real time quantitative reverse transcript ion-polymera se chain reaction. Following chronic L-DOPA treatment of 6-hydroxydopamine- lesioned rats, secretogranin II mRNA was further up-regulated to a similar degree to that observed for preproenkephalin A mRNA expression. Immunohisto chemical analysis confirmed the increase in secretogranin IT peptide levels in striatal neurotics in 6-hydroxydopamine-lesioned rats following chronic L-DOPA treatment, The increase in secretogranin II mRNA occurring following destruction of th e nigro-striatal pathway and chronic L-DOPA treatment may result in an incr ease in secretoneurin levels, which could be important for the regulation o f striatal output pathways. (C) 2001 IBRO. Published by Elsevier Science Lt d. All rights reserved.