Deficiencies of hippocampal Zn and ZnT3 accelerate brain aging of rat

We examined the link of hippocampal Zn to the functional impairments with a ging using senescence-accelerated mouse prone 10 (SAMP10) with deficits in learning and memory. Zn in hippocampal mossy fiber pathway was less distrib uted in aged SAMP10 than that in the age-matched control. Furthermore, expr ession of Zn transporter 3, ZnT3, which plays to accumulate Zn in synaptic vesicles in the mossy fiber pathway, was markedly reduced in the hippocampa l region even in young SAMP10. Moreover, excessive presynaptic release of g lutamate as well as glycine and expression of glial fibrillary acidic prote in, a marker of neuronal cell injury, were observed in the hippocampus of a ged SAMP10 compared to the control. The present results suggest that age-de pendent deficiencies of Zn in synaptic vesicles of the mossy fiber pathway induced by low expression of ZnT3 cause glutamatergic excitotoxicity in the hippocampal neurons and the deterioration of learning and memory in SAMP10 . (C) 2000 Academic Press.