Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing
Abstract
When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions.Citation
PLoS One. 2011 Dec 13; 6(12):e28427ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0028427
Scopus Count
Related articles
- Astrocyte-neuron lactate transport is required for long-term memory formation.
- Authors: Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM
- Issue date: 2011 Mar 4
- Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens.
- Authors: Gibbs ME, Anderson DG, Hertz L
- Issue date: 2006 Aug 15
- Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.
- Authors: Sickmann HM, Walls AB, Schousboe A, Bouman SD, Waagepetersen HS
- Issue date: 2009 May
- Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.
- Authors: Matsui T, Omuro H, Liu YF, Soya M, Shima T, McEwen BS, Soya H
- Issue date: 2017 Jun 13
- Noradrenaline-induced l-lactate production requires d-glucose entry and transit through the glycogen shunt in single-cultured rat astrocytes.
- Authors: Fink K, Velebit J, Vardjan N, Zorec R, Kreft M
- Issue date: 2021 Apr