GSK3β Regulates Brain Energy Metabolism

Cell Reports
Stephen A MartinRozalyn M Anderson

Abstract

GSK3β is a serine threonine kinase implicated in the progression of Alzheimer's disease. Although the role of GSK3β in growth and pathology has been extensively studied, little is known about the metabolic consequences of GSK3β manipulation, particularly in the brain. Here, we show that GSK3β regulates mitochondrial energy metabolism in human H4 neuroglioma cells and rat PC12-derived neuronal cells and that inhibition of GSK3β in mice in vivo alters metabolism in the hippocampus in a region-specific manner. We demonstrate that GSK3β inhibition increases mitochondrial respiration and membrane potential and alters NAD(P)H metabolism. These metabolic effects are associated with increased PGC-1α protein stabilization, enhanced nuclear localization, and increased transcriptional co-activation. In mice treated with the GSK3β inhibitor lithium carbonate, changes in hippocampal energy metabolism are linked to increased PGC-1α. These data highlight a metabolic role for brain GSK3β and suggest that the GSK3β/PGC-1α axis may be important in neuronal metabolic integrity.

Citations

Jul 18, 2019·GeroScience·Dylan C Souder, Rozalyn M Anderson
Nov 21, 2019·Journal of Alzheimer's Disease : JAD·Neha Sawant, P Hemachandra Reddy
Aug 23, 2020·International Journal of Molecular Sciences·Sakulrat MankhongJu-Hee Kang
Jul 13, 2019·Frontiers in Aging Neuroscience·Carolina OsorioAdonis Sfera
Apr 1, 2020·ELife·Simranjot BawaErika R Geisbrecht
May 7, 2020·Frontiers in Neuroscience·Chunmei GengPei Jiang
Feb 2, 2021·Journal of Cellular and Molecular Medicine·Chunmei GuoMing-Zhong Sun
Feb 13, 2021·Cells·Ido Rippin, Hagit Eldar-Finkelman
May 6, 2021·Aging Cell·Dylan C SouderRozalyn M Anderson
Jun 24, 2021·Neuroscience Letters·Monique P SingulaniOrestes V Forlenza

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
transfection
Assay
reverse transcription PCR

Software Mentioned

WiscScan
SPC
LOCI
ImageJ
SPCImage
Adobe Photoshop
SAS

Related Concepts

Related Feeds

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Kai YangLonghuo Wu
International Journal of Cell Biology
Keith M JacobsDinesh Thotala
© 2022 Meta ULC. All rights reserved