ABSTRACT. The tumoral uptake of fluorine-18-deoxyglucose (FDG) is based upon enhanced glycolysis. Following injection, FDG is phosphorylated and trapped intracellularly. An important mechanism to transport FDG into the transformed cell is based upon the action of glucose transporter proteins; furthermore, highly active hexokinase bound to tumor mitochondria helps to trap FDG into the cell. In addition, enhanced FDG uptake may be due to relative hypoxia in tumor masses, which activates the anaerobic glycolytic pathway. In spite of these processes, FDG uptake is relatively aspecific since all living cells need glucose. Clinical use is therefore recommended in carefully selected patients. NUCL MED BIOL 25;4:317-322, 1998.

SUMMARY STAT3 is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature central nervous system (CNS) neurons remain unclear. Here we show that along with nuclear translocation, STAT3 translocates to mitochondria in mature CNS neurons upon cytokine stimulation. Loss- and gain-of-function studies using knockout mice and viral expression of various STAT3 mutants demonstrate that STAT3's transcriptional function is indispensable for CNS axon regrowth whereas mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth. STAT3's localization, functions, and growth-promoting effects are regulated by MEK, an effect further enhanced by Pten deletion leading to extensive axon regrowth in the mouse optic pathway and spinal cord. These results highlight CNS neuronal dependence on STAT3 transcriptional activity with mitochondrial STAT3 providing ancillary roles, and illustrate a critical contribution for MEK in enhancing diverse STAT3 functions and axon regrowth.

Highlights d ipRGCs survive and regenerate axons well after injury d RNA-seq reveals unique sets of genes enriched in injured ipRGCs, including Thbs1 and Sdc1 d Neural THBS1 promotes axon regeneration in various RGC types d Neural THBS1 promotes axon regeneration in a syndecan1dependent manner