Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Caio H MazucantiSimonetta Camandola

Abstract

Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknown. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of FGFR1, Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together, these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons and other cells types as a metabolic substrate.

References

Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·L Pellerin, P J Magistretti
Feb 17, 1998·Biochemical and Biophysical Research Communications·Y MatsumuraY Nabeshima
Mar 25, 2000·Neurochemistry International·W Walz
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Dan E ArkingHarry C Dietz
Oct 5, 2002·Ageing Research Reviews·Yo-ichi Nabeshima
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Taku NagaiToshitaka Nabeshima
Nov 16, 2004·Trends in Neurosciences·Leif Hertz, H Ronald Zielke
Jun 9, 2005·BMC Bioinformatics·Seon-Young Kim, David J Volsky
Aug 27, 2005·Science·Hiroshi KurosuMakoto Kuro-o
Jan 27, 2006·The Journal of Biological Chemistry·Hiroshi KurosuMakoto Kuro-o
Aug 11, 2007·Science·Hongjun LiuToren Finkel
Dec 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ci-Di ChenCarmela R Abraham
Jan 8, 2008·Cell Metabolism·Ralph J DeBerardinisCraig B Thompson
Jul 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Seung-Kuy ChaChou-Long Huang
Feb 24, 2009·Biochimica Et Biophysica Acta·Makoto Kuro-o
Apr 8, 2009·Molecular Pharmacology·Seung-Kuy ChaChou-Long Huang
Sep 10, 2009·FEBS Letters·Laura BlochChristoph Kaether
Oct 22, 2009·Nature Reviews. Endocrinology·M Shawkat Razzaque
Feb 24, 2010·Neurobiology of Learning and Memory·Ewan C McNayRobert S Sherwin
May 27, 2010·The Journal of Biological Chemistry·Jinsook KimSeung T Lim
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrei G VlassenkoMark A Mintun
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·S Neil VaishnaviMarcus E Raichle
Feb 22, 2011·Nature Cell Biology·Feng LiuJun Gu
Mar 8, 2011·Cell·Akinobu SuzukiCristina M Alberini
Oct 1, 2011·Cerebral Cortex·Eduardo D MartínDeborah J Burks
Oct 27, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Luc Pellerin, Pierre J Magistretti
Dec 22, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gerald A Dienel
Dec 23, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paqui G TravésMarta Cascante
Jan 17, 2012·Neurobiology of Aging·Dwight C GermanXinran Liu
Jul 24, 2012·Pharmacology & Therapeutics·William A BanksMichelle A Erickson
Feb 1, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ci-Di ChenCarmela R Abraham

❮ Previous
Next ❯

Citations

Jul 4, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Miled BourourouNicolas Blondeau
Apr 8, 2020·BioResearch Open Access·Walter H MoosXiaohong Chen
Jan 2, 2021·Sleep Medicine·Giuliano da Paz OliveiraFernando Morgadinho Santos Coelho
Jun 22, 2021·Metabolism: Clinical and Experimental·Taylor LandryHu Huang
Nov 7, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ji-Hyun ParkKazuhide Hayakawa
Aug 8, 2021·International Journal of Molecular Sciences·Marlena TypiakAgnieszka Piwkowska
Sep 24, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hong AnXunming Ji
Sep 28, 2021·Translational Stroke Research·Taylor E BranyanFarida Sohrabji

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE
100046

Methods Mentioned

BETA
transgenic
FRET
ELISA
Chip
Feature Extraction
PCR

Software Mentioned

SAM JMP
Feature Extraction
Agilent
DIANE
Graph Pad Prism

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.