Effect of the neurotoxic dose of methamphetamine on gene expression of parkin and Pael-receptors in rat striatum.
We previously reported that haloperidol, a dopamine-D(2) receptor antagonist, induced striatal expression of parkin gene, which mutations cause autosomal recessive juvenile parkinsonism. Because of an involvement of the parkin gene defect in selective degeneration of dopaminergic neurons, we herein examined the effect of the neurotoxic dose of methamphetamine (METH; 40 mg/kg, i.p.) on gene expression of parkin and its substrate Pael-receptor (R) in the dopamine-rich areas of the rat brain, using reverse transcription-polymerase chain reaction. parkin mRNA levels in the striatum, but not in other regions, decreased at 1 and 2 h and returned to the pre-drug basal levels at 4 h after METH administration. METH also decreased Pael-R mRNA levels in the striatum and substantia nigra within 2 h after METH, while haloperidol (2 mg/kg, s.c.) increased Pael-R mRNA levels in the substantia nigra at 2 h after administration. These results suggest that temporary suppression of gene expression of parkin and Pael-R may be associated with the METH-induced dopaminergic neurotoxicity. Taken together with our previous report, dopaminergic modulation of the expression of parkin and Pael-R genes in the nigro-striatal pathway may have significant implication for pathophysiology and treatment of parkinson disease.
Nakahara
T
T
Department of Chemistry, Faculty of Science, Kyushu University, Ropponmatsu, Fukuoka 810-8560, Japan. nakahara@rc.kyushi-u.ac.jp
Kuroki
T
T
Ohta
E
E
Kajihata
T
T
Yamada
H
H
Yamanaka
M
M
Hashimoto
K
K
Tsutsumi
T
T
Hirano
M
M
Uchimura
H
H
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008025:Ligases / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D008694:Methamphetamine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases; D006220:Haloperidol