The mammalian brain is totally dependent on a continuous supply of blood-borne nutrients, primarily glucose, to maintain normal functional activity. The delivery of glucose to the brain is mediated by the facilitative glucose transporter proteins (GLUTs). In certain conditions, e.g. during development, fasting, and diabetes, the brain can utilize alternative substrates such as the ketone bodies and lactic acid. Lactate has also been suggested to be important in metabolic trafficking between neurons and glia. The transport of these substances is mediated by a newly emerging family of membrane transporters, the monocarboxylate transporters (MCTs).We have recently cloned and generated antibodies against mouse MCT8 and using a combination of in situ hybridization and immunohistochemistry demonstrated it has a profoundly different cellular localization in rat and mouse brain to MCT1 and MCT2. MCT8 is found at high levels in the choroid plexus, in neurons of the hippocampus, particularly at the neonatal day 7, and in neurons in layer 2 of the cortex. We are currently attempting to express the protein in yeast in order to characterize it activity and substrate specificity.The GLUT4 glucose transporter isoform is the predominant transporter in heart, skeletal muscle and adipose tissue where its activity is regulated by insulin and contraction. Earlier studies from our laboratory have also found it to be expressed in adult rodent brain in granule cell of the cerebellum, hippocampus, and olfactory bulb. Recent studies investigating its role in granule cell neurogenisis revealed GLUT4 mRNA and protein to be expressed during embryogenisis in the mouse. We detected GLUT4 protein as early as embryonic day 9 in both neural and non-neural tissues and to exhibit a very specific spatio-temporal pattern of expression. For example, it is extensively expressed in endocardial cushions of the developing heart at E10-12 but rapidly decreases thereafter and expression remains very low until its characteristic postnatal increase. These observations suggest new role(s) for GLUT4 in the developing embryo. - Brain Glucose Nutrient Transporters Lactate Ischemia
