Distribution of metallothionein I + II and vesicular zinc in the developing central nervous system: correlative study in the rat.

Because zinc (Zn) is a co-factor in enzymes and participates in neurotransmission, it is essential for brain development. However, because excess Zn may cause neuronal injury, cerebral mechanisms for Zn regulation must operate. The metallothionein isoforms I and II (MT I + II) are putative candidates for chelating unbound Zn released from Zn-containing nerve terminals or transported into the brain. Whether vesicular Zn and MT I + II occur in identical regions of the developing brain is unknown. Accordingly, the developmental distribution of MT I + II and vesicular Zn was mapped. By using double-labeling fluorescence histochemistry, MT I + II immunoreactivity (ir) was attributed to astrocytes and cells of myelomonocytic lineage. The cells of the myelomonocytic lineage shared the morphology of monocytes and macrophages but not of microglia and occurred primarily around vessels and ventricles in the brainstem. By contrast, astrocytes were widespread throughout the developing brain. In embryonic and neonatal brain, MT I + IIir astrocytes were almost selectively observed in the septum and fascia dentate hilus (hi) of the hippocampus. With increasing postnatal age, they also occurred in hippocampal cortex, basal forebrain, neocortex, cerebellar cortex, and cranial nerve nuclei. MT I + II mRNAs were detected in regions of the brain that also displayed MT I + IIir, indicating transcriptional events. Vesicular Zn was recorded in neonatal brain solely in the dentate hi of the hippocampus. With increasing age, the amount of vesicular Zn increased in the hippocampus and other forebrain regions. The presence of MT I + II proteins in the developing brain was confirmed by radioimmunoassay. The regional distribution of astrocytic MT I + IIir and vesicular Zn suggests that MT I + II are implicated in Zn metabolism in the developing forebrain. Copyright 1999 Wiley-Liss, Inc.