Developmental regulation of genes mediating murine brain glucose uptake

We examined the molecular mechanisms that mediate the developmental increas e in murine whole brain 2-deoxyglucose uptake. Northern and Western blot an alyses revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3 (neuronal) membrane-spanning facilitative glucose tr ansporter mRNA and protein concentrations. Nuclear run-on experiments revea led that these developmental changes in GLUT-1 and -3 were regulated posttr anscriptionally. In contrast, the mRNA and protein levels of the mitochondr ially bound glucose phosphorylating hexokinase I enzyme were unaltered. How ever, hexokinase I enzyme activity increased in an age-dependent manner sug gestive of a posttranslational modification that is necessary for enzymatic activation. Together, the postnatal increase in GLUT-1 and -3 concentratio ns and hexokinase I enzymatic activity led to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the molecular mechanisms regulating t he increase in the three different gene products may vary, the age-dependen t increase of all three constituents appears essential for meeting the incr easing demand of the maturing brain to fuel the processes of cellular growt h, differentiation, and neurotransmission.