Premium
Regulation of GAP‐43 protein and mRNA in nigrostriatal dopaminergic neurons after the partial destruction of dopaminergic terminals with intrastriatal 6‐hydroxydopamine
Author(s) -
Iwata ShinIchi,
Nomoto Masahiro,
Fukuda Takeo
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20010101)39:1<16::aid-syn3>3.0.co;2-#
Subject(s) - hydroxydopamine , dopaminergic , neuroscience , nigrostriatal pathway , dopamine , dopaminergic pathways , parkinson's disease , biology , medicine , substantia nigra , disease
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. Synapse 39:16–22, 2001. © 2001 Wiley‐Liss, Inc.