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 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.
Medhurst
A D
AD
Neuroscience Research, GlaxoSmithKline, Harlow, Essex, UK. andy_medhurst-1@sbphrd.com
Zeng
B Y
BY
Charles
K J
KJ
Gray
J
J
Reavill
C
C
Hunter
A J
AJ
Shale
J A
JA
Jenner
P
P
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002864:Chromogranins; D018076:DNA, Complementary / Q000032:analysis; D018491:Dopamine Agonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053381:Secretogranin II; D013565:Sympatholytics / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D002864:Chromogranins; D018076:DNA, Complementary; D018491:Dopamine Agonists; D009479:Neuropeptides; D011506:Proteins; D012333:RNA, Messenger; D053381:Secretogranin II; D013565:Sympatholytics; C081159:secretoneurin; D007980:Levodopa; D016627:Oxidopamine; D001058:Apomorphine