Postnatal regulation of ZnT-1 expression in the mouse brain

We have characterized the postnatal development of ZnT-1, a putative zinc transporter, in the mouse brain with respect to chelatable zinc in four distinct brain areas: cerebral cortex, hippocampus, olfactory bulb and cerebellum. At birth, both zinc and ZnT-1 immunoreactivity were nearly undetectable. Beginning at the end of the first postnatal week, ZnT-1 expression increased significantly in all areas examined except the cerebellum, which contains virtually no synaptic zinc. Moreover, neurons immunoreactive for ZnT-1 were typically present in areas rich in synaptic zinc, which increased in parallel with ZnT-1. In the cerebellum, in contrast, Purkinje cells exhibited robust immunoreactivity for ZnT-1 only in the second postnatal week. While the parallel development of zinc and ZnT-1 in forebrain regions supports a direct role for synaptic zinc in regulating ZnT-1 expression, ZnT-1 in cerebellar Purkinje cells could indicate that expression of this zinc transporter may also be regulated by a non-synaptic pool of zinc or by other mechanism(s). The striking developmental regulation of ZnT-1 expression together with synaptic zinc indicates that ZnT-1 may play a key role in protecting developing neurons against potentially toxic zinc. (C) 2002 Elsevier Science B.V. All rights reserved.