Up-regulation of Secretoneurin Immunoreactivity and Secretogranin II Mrna in Rat Striatum Following 6-Hydroxydopamine Lesioning and Chronic L-DOPA Treatment.

AD Medhurst,BY Zeng,KJ Charles,J Gray,C Reavill,AJ Hunter,JA Shale,P Jenner

Neuroscience（2001）SCI 3区

GlaxoSmithKline | Neurodegenerative Diseases Research Centre | Neuroscience Research

Cited 13|Views5

Abstract

Destruction of the nigro-striatal pathway in Parkinson's disease and treatment with L-DOPA lead to persistent alterations in basal ganglia output pathways that are poorly characterised. Differential display mRNA analysis was used to study the effects of 6-hydroxydopamine-induced lesions of the medial forebrain bundle on gene expression in the rat striatum. One up-regulated cDNA identified in two independent groups of 6-hydroxydopamine-lesioned animals was cloned and sequence analysis showed 97% homology to secretogranin II. Differential up-regulation of secretogranin II following 6-hydroxydopamine lesioning was confirmed in a further group of 6-hydroxydopamine-lesioned rats using TaqMan real time quantitative reverse transcription-polymerase 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. Immunohistochemical analysis confirmed the increase in secretogranin II peptide levels in striatal neurones in 6-hydroxydopamine-lesioned rats following chronic L-DOPA treatment. The increase in secretogranin II mRNA occurring following destruction of the nigro-striatal pathway and chronic L-DOPA treatment may result in an increase in secretoneurin levels, which could be important for the regulation of striatal output pathways.

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Key words

nigral-striatal pathway,differential display,up-regulation,TaqMan,gene expression

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