Ontogeny and cellular distribution of brain glucose transporter gene expression.

Patterns of gene expression for the facilitative glucose transporters 1-4 (GTs 1-4) were mapped using in situ hybridization on rat brains from embryonic day 11 (E 11) through adulthood. GT2 and GT4 mRNAs were not detected at any stage of development. Prior to the formation of the blood-brain barrier (BBB), GT1 mRNA was localized in the germinal neuroepithelium. During and after formation of the BBB, GT1 mRNA was abundant in brain and spinal cord vascular endothelium and in condensations of mesenchyme forming the meninges. With the gradual disappearance of the germinal neuroepithelium, GT1 mRNA was retained in the ependymal cell layer lining the ventricles. Postnatally, GT1 mRNA appeared in numerous small parenchymal cells, demonstrating characteristic glial cell morphology and distribution, and was not detected in neurons. GT3 mRNA, in contrast, was detected only in differentiated neurons, indicating that there is a switch from GT1 to GT3 gene expression by neuroepithelial cell lineages during the process of terminal neural differentiation. GT3 mRNA increased gradually from E14, attaining adult levels in most regions by postnatal day 20. The highest levels were found in large projection neurons of the olfactory system, hippocampal formation, neocortex (VI), and deep cerebellar, pontine, and brain stem nuclei. The ontogeny and neuroanatomical distribution of GT3 gene expression correlates with developmental and regional patterns of brain glucose utilization, suggesting that-while GT1 may have a role in the transfer of glucose across the BBB-GT3 expression determines brain glucose utilization.