Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metallothionein-I and -II knock-out mouse brain.
The effects of two major isoforms of metallothioneins (MTs), MT-I and -II, on dopaminergic neurotoxicity of 6-hydroxydopamine (6-OHDA) were examined using intracerebroventricularly 6-OHDA-injected MT-I, II knock-out (KO) mice. The loss of dopamine neurons in the substantia nigra pars compacta induced by the 6-OHDA injection was significantly aggravated in the MT-I, II KO mice, compared with that in the 6-OHDA-injected wild-type mice. The present results, taken together with the antioxidant properties of MT-I and -II suggest that MT-I and -II exert neuroprotective effects against the dopaminergic neurotoxicity of 6-OHDA at the nigral cell body by scavenging free radicals.
Asanuma
Masato
M
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama 700-8558, Japan. asachan@cc.okayama-u.ac.jp
Miyazaki
Ikuko
I
Higashi
Youichirou
Y
Tanaka
Ken-ichi
K
Haque
Md Emdadul
ME
Fujita
Naoko
N
Ogawa
Norio
N
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001927:Brain Diseases / Q000201:enzymology* / Q000473:pathology; D003714:Denervation; D050483:Dopamine Plasma Membrane Transport Proteins; D007276:Injections, Intraventricular; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D016627:Oxidopamine; D017382:Reactive Oxygen Species / Q000378:metabolism; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D013565:Sympatholytics; D016627:Oxidopamine; D008668:Metallothionein; D014446:Tyrosine 3-Monooxygenase