title: Regulation of GAP-43 protein and mRNA in nigrostriatal dopaminergic neurons after the partial destruction of dopaminergic terminals with intrastriatal 6-hydroxydopamine.
abstract: Changes in the level of GAP-43 and its mRNA in nigrostriatal dopaminergic neurons in an animal model of the presymptomatic period of Parkinson's disease were measured to find the characteristic features of GAP-43 in nigrostriatal dopaminergic neurons. Since the dopaminergic neurons possess a relatively large amount of GAP-43 protein and mRNA, the dopaminergic neurons must be endowed with specific functions related to those of GAP-43. In this study, dopaminergic axon terminals were partially destroyed by intrastriatal 6-hydroxydopamine (6-OHDA). Rats were decapitated 3, 14, and 56 days following treatment. Levels of GAP-43 and tyrosine hydroxylase (TH) in the striatum were detected by immunoblotting and quantified. The number of GAP-43 mRNA-positive neurons and that of TH mRNA-positive neurons in the substantia nigra pars compacta (SNc) were detected by in situ hybridization using alkaline phosphatase (ALP)-labeled probes. Levels of GAP-43 in the striatum showed no significant alteration during the period of the experiment, although levels of TH were gradually restored. The number of GAP-43 mRNA-positive neurons as well as that of TH mRNA-positive neurons in the SNc decreased. These results suggests that dopaminergic neurons restore their axon terminals with little change in GAP-43, and that transcription and/or stability of GAP-43 mRNA in the dopaminergic neurons are susceptible to the toxin, although the dopaminergic neurons can maintain the translational product in the terminals. This feature may be related with a degeneration of dopaminergic neurons in Parkinson's disease.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. shinichi@m.kufma-u.ac.jp
authors.forename: S I
authors.initials: SI
authors.lastname: Iwata
authors.forename: M
authors.initials: M
authors.lastname: Nomoto
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002452:Cell Count / Q000706:statistics & numerical data; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D019922:GAP-43 Protein / Q000235:genetics*; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016627:Oxidopamine / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D019922:GAP-43 Protein; D012333:RNA, Messenger; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine