Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice

by Petit J.M., Gyger J., Burlet-Godinot S., Fiumelli H., Martin J.L., Magistretti P.J.
Year: 2013 ISSN: DOI: 10.5665/sleep.3034

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Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice
Petit J.M., Gyger J., Burlet-Godinot S., Fiumelli H., Martin J.L., Magistretti P.J.
Sleep, 2013 Oct 1; 36(10):1445-58

Abstract

Pub_GIA_2013​Study Objectives: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifcally in astrocytes following sleep deprivation. Astrocytes were purifed by fuorescence-activated cell sorting from transgenic mice expressing the green fuorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. Design: 6-hour instrumental sleep deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a modifed cage where animals were gently forced to move. Measurements and Results: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, a-2-Na/K pump, Glt1, and Ldha mRNAs were signifcantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not signifcant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. Conclusions: This study shows that TSD induces the expression of genes associated with ANLS specifcally in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

Keywords

Energy metabolism Fow cytometry Glia Glucose Glutamate Transgenic mice