Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain

Israel Sekler, Arie Moran, Michal Hershfinkel, Amir Dori, Ariel Margulis, Nurit Birenzweig, Yuval Nitzan, William F. Silverman

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Zinc maintains a diverse array of functions in the mammalian central nervous system as a key component of numerous enzymes, via its role in the activation of transcription factors, and as a neuroregulator, modulating neuronal receptors such as N-methyl-D-aspartate and γ-aminobutyric acid. Zinc has a dark side, however, with massive influx of Zn2+ to neurons considered to be a key factor in neuronal death secondary to ischemia and seizure. Several different putative zinc transporters, ZnT-1-4, have recently been identified and characterized. Among them, ZnT-1 has been suggested to play a key role in reducing cellular Zn2+ toxicity. In the present study, we describe the regional and cellular distribution of ZnT-1 in the adult mouse brain using an antibody raised against the C-terminal domain of mouse ZnT-1. The distribution of ZnT-1 was compared to that of chelatable Zn2+, visualized by means of neoTimm histochemistry or N-(6-methoxy-8-quinolyl)-p-toluene-sulfonamide (TSQ) histofluorescence. Extracts from various brain regions specifically stained a 60-kDa peptide corresponding to the expected molecular weight of ZnT-1. The expression of ZnT-1 was highest in the cerebral cortex and cerebellum, moderate in the hippocampus, hypothalamus, and olfactory bulb, and lowest in the striatum and septum. In brain sections, ZnT-1-immunoreactive neurons, in particular principle neurons, in the somatosensory cortex, hippocampus, and olfactory bulb, were closely related to synaptic Zn2+. Robust ZnT-1 immunoreactivity was also observed in cerebellar Purkinje cells. Although the function of the protein in these cells is unclear, in the forebrain, ZnT-1 is strikingly present in cells and regions where significant Zn2+ homeostasis is required. This finding suggests a protective role for neuronal ZnT-1 in the context of both normal and pathophysiological activity.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalJournal of Comparative Neurology
Volume447
Issue number3
DOIs
StatePublished - 3 Jun 2002

Keywords

  • Metallothionein
  • Transition metals
  • Zinc-containing neuron

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