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

Abstract

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 specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent 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 modified 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, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, 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 specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

• Authors: Jean-Marie Petit, Joël Gyger, Sophie Burlet-Godinot, Hubert Fiumelli, Jean-Luc Martin, Pierre J Magistretti
• Journal: Sleep (Sleep) Vol. 36 Issue 10 Pg. 1445-58 (Oct 01 2013) ISSN: 1550-9109 [Electronic] United States
• PMID: 24082304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lactates
• Green Fluorescent Proteins

Topics

• Animals
• Astrocytes (metabolism, physiology)
• Electroencephalography
• Electromyography
• Female
• Gene Expression Regulation (genetics, physiology)
• Genes (physiology)
• Green Fluorescent Proteins
• Lactates (metabolism)
• Male
• Mice
• Mice, Transgenic
• Motor Activity
• Sleep (genetics, physiology)
• Sleep Deprivation (genetics, physiopathology)
• Wakefulness (genetics, physiology)