The effect of gender and the neurotrophin, BDNF, upon methamphetamine-induced neurotoxicity of the nigrostriatal dopaminergic system in mice.
The interactive effects between gender and a selective alteration in the neurotrophin, brain-derived neurotrophic factor (BDNF) upon methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic (NSDA) system were assessed. MA treatment produced a greater degree of NSDA neurotoxicity (indicated by greater reductions in corpus striatal dopamine levels) in wild type control BDNF male versus female mice. This sex difference was unaltered in heterozygous mutant BDNF (BDNF +/-) mice and in mice which overexpress BDNF (DBH:BDNF +). Both BDNF mutant conditions resulted in preservation of corpus striatal dopamine levels following MA treatment as compared with their respective MA-treated wild type controls. The relative amount of this preservation was greater in male BDNF mutants, with values being significantly greater than females in the BDNF +/- condition. These results suggest that alterations in BDNF do not alter basic gender differences in MA-induced NSDA neurotoxicity, but may produce a neuroprotection against MA which is relatively greater in males.
Dluzen
Dean E
DE
Department of Anatomy, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA. ded@neoucom.edu
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000506:poisoning; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000506:poisoning*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism*; D012737:Sex Factors; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D004298:Dopamine