Age-related changes in expression of metallothionein-III in rat brain

Metallothionein (MT)-III is a metal binding protein, called growth inhibitory factor, and is mainly expressed in the central nervous system. Since MT-III decreases in the brain of Alzheimer's disease (AD), a growing interest has been focused on its relationship to neurodegenerative diseases. To clarify age-related changes in the MT-III expression and its inducibility against oxidative stress, we analyzed the expression of MT-III and its mRNA in the brain of lipopolysaccharide (LPS)-treated aged rats. In the frontal cortex, basal expression of MT-III mRNA was significantly increased with aging, while it was observed no induction of MT-III mRNA against LPS administration in the aged rat brain. MT-III immunopositive cells were increased in the frontal, parietal and piriform cortices, hypothalamus and amygdaloid nucleus with aging. The LPS treatment induced MT-III expression in the brain of young-adult rats, but not in the aged rat brain. Furthermore, the MT-III induction with LPS treatment was mainly observed in oligodendrocyte and microglia. In the present study, we showed that inducibility of brain MT-III against oxidative stress may be reduced with aging. Since it has been reported that MT-III has neuroprotective roles as an antioxidant, present results suggest that MT-III is closely related to the neurodegeneration in the aged animals.