Metallothionein-III knockout mice aggravates the neuronal damage after transient focal cerebral ischemia.

Abstract

Metallothioneins (MTs) are metal-binding proteins and have four isoforms. MT-III was, at first, found in the brains of patients with Alzheimer's disease. MT-III exists mainly in the central nervous system, and the main effects are thought to be anti-oxidative and regulate zinc levels. In some previous reports, MT-III exhibited neuroprotective effects in various pathological situations, but its detailed effects are still unclear. In the present study, we examined neuronal damage after a middle cerebral artery occlusion (MCAO) in MT-III knockout (KO) mice to elucidate the relationship between MT-III and cerebral infarction. There was no significant difference in cerebral infarction after 24-h permanent MCAO between the wild-type and MT-III KO mice. On the other hand, after 2-h MCAO and 22-h reperfusion, cerebral infarction in the MT-III KO mice was aggravated compared with the wild-type mice. Furthermore, fatal rate of MT-III KO mice increased from 3 days after MCAO, and neurological deficits at 5 and 7 days after MCAO of MT-III KO mice were worse than those of wild-type. We examined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and the immunostaining of an oxidative stress marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG), at 24 h after transient MCAO. In the penumbra lesion, the positive cell numbers in both staining assays were higher in the MT-III KO mice than those of the wild-type mice. These findings indicate that neuronal damage was aggravated by reperfusion injury in the MT-III KO mice compared with the wild-type mice, suggesting that MT-III plays anti-oxidative and neuroprotective roles in transient cerebral ischemia.

• Authors: Akihiro Koumura, Junya Hamanaka, Masamitsu Shimazawa, Akiko Honda, Kazuhiro Tsuruma, Yoko Uchida, Isao Hozumi, Masahiko Satoh, Takashi Inuzuka, Hideaki Hara
• Journal: Brain research (Brain Res) Vol. 1292 Pg. 148-54 (Oct 06 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19635467 (Publication Type: Journal Article)

Chemical References

• Metallothionein 3
• Nerve Tissue Proteins
• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Brain (pathology, physiopathology)
• Cell Count
• Deoxyguanosine (analogs & derivatives)
• Female
• In Situ Nick-End Labeling
• Infarction, Middle Cerebral Artery (mortality, pathology, physiopathology)
• Male
• Metallothionein 3
• Mice
• Mice, Inbred Strains
• Mice, Knockout
• Nerve Tissue Proteins (deficiency, genetics, metabolism)
• Neurons (pathology, physiology)
• Random Allocation
• Reperfusion Injury (mortality, pathology, physiopathology)
• Time Factors