Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metallothionein-I and -II knock-out mouse brain

Masato Asanuma; Ikuko Miyazaki; Youichirou Higashi; Ken Ichi Tanaka; Md Emdadul Haque; Naoko Fujita; Norio Ogawa

doi:10.1016/S0304-3940(02)00346-4

Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metallothionein-I and -II knock-out mouse brain

Masato Asanuma, Ikuko Miyazaki, Youichirou Higashi, Ken Ichi Tanaka, Md Emdadul Haque, Naoko Fujita, Norio Ogawa

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	61-65
Number of pages	5
Journal	Neuroscience Letters
Volume	327
Issue number	1
DOIs	https://doi.org/10.1016/S0304-3940(02)00346-4
Publication status	Published - Jul 12 2002

Keywords

6-Hydroxydopamine
Dopamine
Dopamine transporter
Knock-out mouse
Metallothionein
Reactive oxygen species
Tyrosine hydroxylase

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0304-3940(02)00346-4

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title = "Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metallothionein-I and -II knock-out mouse brain",

abstract = "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.",

keywords = "6-Hydroxydopamine, Dopamine, Dopamine transporter, Knock-out mouse, Metallothionein, Reactive oxygen species, Tyrosine hydroxylase",

author = "Masato Asanuma and Ikuko Miyazaki and Youichirou Higashi and Tanaka, {Ken Ichi} and Haque, {Md Emdadul} and Naoko Fujita and Norio Ogawa",

note = "Funding Information: This work was supported in part by Grants-in-Aid for Scientific Research (C) and for the Encouragement of Young Scientists (A) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and by Grants-in Aid for Research on Pharmaceutical and Medical Safety, for Research on Brain Science, and for Research on Specific Diseases from the Japanese Ministry of Health, Labour and Welfare. The authors thank the staff at the Animal Center for Medical Research of Okayama University Medical School for their impeccable care of the experimental animals.",

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AU - Asanuma, Masato

AU - Miyazaki, Ikuko

AU - Higashi, Youichirou

AU - Tanaka, Ken Ichi

AU - Haque, Md Emdadul

AU - Fujita, Naoko

AU - Ogawa, Norio

N1 - Funding Information: This work was supported in part by Grants-in-Aid for Scientific Research (C) and for the Encouragement of Young Scientists (A) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and by Grants-in Aid for Research on Pharmaceutical and Medical Safety, for Research on Brain Science, and for Research on Specific Diseases from the Japanese Ministry of Health, Labour and Welfare. The authors thank the staff at the Animal Center for Medical Research of Okayama University Medical School for their impeccable care of the experimental animals.

PY - 2002/7/12

Y1 - 2002/7/12

N2 - 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.

AB - 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.

KW - 6-Hydroxydopamine

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KW - Dopamine transporter

KW - Knock-out mouse

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KW - Tyrosine hydroxylase

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Aggravation of 6-hydroxydopamine-induced dopaminergic lesions in metallothionein-I and -II knock-out mouse brain

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