Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet 2014 Dec 15;23(24):6528-41
Date
07/17/2014Pubmed ID
25027327Pubmed Central ID
PMC4271074DOI
10.1093/hmg/ddu371Scopus ID
2-s2.0-84938655903 (requires institutional sign-in at Scopus site) 98 CitationsAbstract
Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1α, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor κB nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis.
Author List
Wilkins HM, Harris JL, Carl SM, E L, Lu J, Eva Selfridge J, Roy N, Hutfles L, Koppel S, Morris J, Burns JM, Michaelis ML, Michaelis EK, Brooks WM, Swerdlow RHAuthor
Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AMP-Activated Protein KinasesAnimals
DNA-Binding Proteins
Electron Transport Complex IV
Gene Expression Regulation
Glutathione
High Mobility Group Proteins
Hippocampus
Inflammation
Injections, Intraperitoneal
Insulin
Lactic Acid
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins
Mitochondria
Mitochondrial Turnover
Neurogenesis
Neuropeptides
Nuclear Respiratory Factor 1
Oxaloacetic Acid
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Signal Transduction
Transcription Factors
gamma-Aminobutyric Acid
p38 Mitogen-Activated Protein Kinases
