GSK3? Regulates Brain Energy Metabolism.

ABSTRACT: GSK3? is a serine threonine kinase implicated in the progression of Alzheimer's disease. Although the role of GSK3? in growth and pathology has been extensively studied, little is known about the metabolic consequences of GSK3? manipulation, particularly in the brain. Here, we show that GSK3? regulates mitochondrial energy metabolism in human H4 neuroglioma cells and rat PC12-derived neuronal cells and that inhibition of GSK3? in mice in vivo alters metabolism in the hippocampus in a region-specific manner. We demonstrate that GSK3? inhibition increases mitochondrial respiration and membrane potential and alters NAD(P)H metabolism. These metabolic effects are associated with increased PGC-1? protein stabilization, enhanced nuclear localization, and increased transcriptional co-activation. In mice treated with the GSK3? inhibitor lithium carbonate, changes in hippocampal energy metabolism are linked to increased PGC-1?. These data highlight a metabolic role for brain GSK3? and suggest that the GSK3?/PGC-1? axis may be important in neuronal metabolic integrity.

SUBMITTER: Martin SA 

PROVIDER: S-EPMC6082412 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other