Distribution of metallothionein I plus 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 neurotransm ission, it is essential for brain development. However, because excess Zn m ay cause neuronal injury, cerebral mechanisms for Zn regulation must operat e. The metallothionein isoforms I and II (MT I + II) are putative candidate s for chelating unbound Zn released from Zn-containing nerve terminals or t ransported into the brain. Whether vesicular Zn and MT I + II occur in iden tical regions of the developing brain is unknown. Accordingly, the developm ental distribution of MT I + II and vesicular Zn was mapped. By using doubl e-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 macropha ges but not of microglia and occurred primarily around vessels and ventricl es 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 cran ial nerve nuclei. MT I + II mRNAs were detected in regions of the brain tha t also displayed MT I + IIir, indicating transcriptional events. Vesicular Zn was recorded in neonatal brain solely in the dentate hi of the hippocamp us. With increasing age, the amount of vesicular Zn increased in the hippoc ampus and other forebrain regions. The presence of MT I + II proteins in th e developing brain was confirmed by radioimmunoassay. The regional distribu tion of astrocytic MT I + IIir and vesicular Zn suggests that MT I + II are implicated in Zn metabolism in the developing forebrain. J. Comp. Neurol. 412:303-318, 1999. (C) 1999 Wiley-Liss, Inc.