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Glucose Tightly Controls Morphological and Functional Properties of Astrocytes.

Lee CY, Dallérac G, Ezan P, Anderova M, Rouach N - Front Aging Neurosci (2016)

Bottom Line: Electrophysiological recordings of hippocampal astroglial cells of the stratum radiatum in situ revealed that shortage of glucose specifically increases astrocyte membrane capacitance, whilst it has no impact on other passive membrane properties.Consistent with this change, morphometric analysis unraveled a prompt increase in astrocyte volume upon glucose deprivation.Furthermore, characteristic functional properties of astrocytes are also affected by transient glucose deficiency.

View Article: PubMed Central - PubMed

Affiliation: Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique UMR 7241, Institut National de la Santé et de la Recherche Médicale U1050, Labex Memolife, PSL Research University Paris, France.

ABSTRACT
The main energy source powering the brain is glucose. Strong energy needs of our nervous system are fulfilled by conveying this essential metabolite through blood via an extensive vascular network. Glucose then reaches brain tissues by cell uptake, diffusion and metabolization, processes primarily undertaken by astrocytes. Deprivation of glucose can however occur in various circumstances. In particular, ageing is associated with cognitive disturbances that are partly attributable to metabolic deficiency leading to brain glycopenia. Despite the crucial role of glucose and its metabolites in sustaining neuronal activity, little is known about its moment-to-moment contribution to astroglial physiology. We thus here investigated the early structural and functional alterations induced in astrocytes by a transient metabolic challenge consisting in glucose deprivation. Electrophysiological recordings of hippocampal astroglial cells of the stratum radiatum in situ revealed that shortage of glucose specifically increases astrocyte membrane capacitance, whilst it has no impact on other passive membrane properties. Consistent with this change, morphometric analysis unraveled a prompt increase in astrocyte volume upon glucose deprivation. Furthermore, characteristic functional properties of astrocytes are also affected by transient glucose deficiency. We indeed found that glucoprivation decreases their gap junction-mediated coupling, while it progressively and reversibly increases their intracellular calcium levels during the slow depression of synaptic transmission occurring simultaneously, as assessed by dual electrophysiological and calcium imaging recordings. Together, these data indicate that astrocytes rapidly respond to metabolic dysfunctions, and are therefore central to the neuroglial dialog at play in brain adaptation to glycopenia.

No MeSH data available.


Related in: MedlinePlus

Glucose deficiency impairs astrocyte gap junctional coupling. (A) Sample images of gap junction-mediated biocytin coupling in CA1 stratum radiatum astrocytes from slices perfused with 30 min with control or 0 glucose ACSF. Scale bar, 50 μm. (B) Gap-junction coupling is significantly reduced following 30 min glucose deprivation, as quantified by counting the number of coupled cells following biocytin injection of a single astrocyte through a patch pipette in slices perfused with control (n = 5 slices, 3 mice) and 0 glucose ACSF (n = 5 slices, 3 mice, p < 0.05). (C–D) Western blot analysis of Cx43 and Cx30 (C), GFAP and vimentin (D) in hippocampal slices exposed to control (n = 3 mice) and glucose-free ACSF for 30 min (n = 3 mice), showing no alteration in total protein levels. Asterisks indicate statistical significance (*p < 0.05).
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Figure 3: Glucose deficiency impairs astrocyte gap junctional coupling. (A) Sample images of gap junction-mediated biocytin coupling in CA1 stratum radiatum astrocytes from slices perfused with 30 min with control or 0 glucose ACSF. Scale bar, 50 μm. (B) Gap-junction coupling is significantly reduced following 30 min glucose deprivation, as quantified by counting the number of coupled cells following biocytin injection of a single astrocyte through a patch pipette in slices perfused with control (n = 5 slices, 3 mice) and 0 glucose ACSF (n = 5 slices, 3 mice, p < 0.05). (C–D) Western blot analysis of Cx43 and Cx30 (C), GFAP and vimentin (D) in hippocampal slices exposed to control (n = 3 mice) and glucose-free ACSF for 30 min (n = 3 mice), showing no alteration in total protein levels. Asterisks indicate statistical significance (*p < 0.05).

Mentions: One important property of astrocytes enabling them to spread metabolites across the neuropil is the high intercellular coupling they achieve through gap junctions. To assess whether shortage of the primary metabolite glucose affects the strong intercellular communication that takes place between hippocampal astrocytes, we infused biocytin, a low molecular weight tracer permeable to gap junction channels, specifically into a single astrocyte via a patch pipette during 30 min of glucose deprivation or regular ACSF (control). We observed an extensive intercellular diffusion of biocytin into the gap-junction mediated astroglial network, reaching more than 200 cells in control conditions (207.4 ± 30.0, n = 5). Remarkably, shortage of glucose during this relatively short period was sufficient to markedly reduce astroglial coupling, as the number of coupled cells significantly decreased by ~44% (117.4 ± 9.7, n = 5; p < 0.05; Figures 3A,B).


Glucose Tightly Controls Morphological and Functional Properties of Astrocytes.

Lee CY, Dallérac G, Ezan P, Anderova M, Rouach N - Front Aging Neurosci (2016)

Glucose deficiency impairs astrocyte gap junctional coupling. (A) Sample images of gap junction-mediated biocytin coupling in CA1 stratum radiatum astrocytes from slices perfused with 30 min with control or 0 glucose ACSF. Scale bar, 50 μm. (B) Gap-junction coupling is significantly reduced following 30 min glucose deprivation, as quantified by counting the number of coupled cells following biocytin injection of a single astrocyte through a patch pipette in slices perfused with control (n = 5 slices, 3 mice) and 0 glucose ACSF (n = 5 slices, 3 mice, p < 0.05). (C–D) Western blot analysis of Cx43 and Cx30 (C), GFAP and vimentin (D) in hippocampal slices exposed to control (n = 3 mice) and glucose-free ACSF for 30 min (n = 3 mice), showing no alteration in total protein levels. Asterisks indicate statistical significance (*p < 0.05).
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Figure 3: Glucose deficiency impairs astrocyte gap junctional coupling. (A) Sample images of gap junction-mediated biocytin coupling in CA1 stratum radiatum astrocytes from slices perfused with 30 min with control or 0 glucose ACSF. Scale bar, 50 μm. (B) Gap-junction coupling is significantly reduced following 30 min glucose deprivation, as quantified by counting the number of coupled cells following biocytin injection of a single astrocyte through a patch pipette in slices perfused with control (n = 5 slices, 3 mice) and 0 glucose ACSF (n = 5 slices, 3 mice, p < 0.05). (C–D) Western blot analysis of Cx43 and Cx30 (C), GFAP and vimentin (D) in hippocampal slices exposed to control (n = 3 mice) and glucose-free ACSF for 30 min (n = 3 mice), showing no alteration in total protein levels. Asterisks indicate statistical significance (*p < 0.05).
Mentions: One important property of astrocytes enabling them to spread metabolites across the neuropil is the high intercellular coupling they achieve through gap junctions. To assess whether shortage of the primary metabolite glucose affects the strong intercellular communication that takes place between hippocampal astrocytes, we infused biocytin, a low molecular weight tracer permeable to gap junction channels, specifically into a single astrocyte via a patch pipette during 30 min of glucose deprivation or regular ACSF (control). We observed an extensive intercellular diffusion of biocytin into the gap-junction mediated astroglial network, reaching more than 200 cells in control conditions (207.4 ± 30.0, n = 5). Remarkably, shortage of glucose during this relatively short period was sufficient to markedly reduce astroglial coupling, as the number of coupled cells significantly decreased by ~44% (117.4 ± 9.7, n = 5; p < 0.05; Figures 3A,B).

Bottom Line: Electrophysiological recordings of hippocampal astroglial cells of the stratum radiatum in situ revealed that shortage of glucose specifically increases astrocyte membrane capacitance, whilst it has no impact on other passive membrane properties.Consistent with this change, morphometric analysis unraveled a prompt increase in astrocyte volume upon glucose deprivation.Furthermore, characteristic functional properties of astrocytes are also affected by transient glucose deficiency.

View Article: PubMed Central - PubMed

Affiliation: Neuroglial Interactions in Cerebral Physiopathology, Center for Interdisciplinary Research in Biology, Collège de France, Centre National de la Recherche Scientifique UMR 7241, Institut National de la Santé et de la Recherche Médicale U1050, Labex Memolife, PSL Research University Paris, France.

ABSTRACT
The main energy source powering the brain is glucose. Strong energy needs of our nervous system are fulfilled by conveying this essential metabolite through blood via an extensive vascular network. Glucose then reaches brain tissues by cell uptake, diffusion and metabolization, processes primarily undertaken by astrocytes. Deprivation of glucose can however occur in various circumstances. In particular, ageing is associated with cognitive disturbances that are partly attributable to metabolic deficiency leading to brain glycopenia. Despite the crucial role of glucose and its metabolites in sustaining neuronal activity, little is known about its moment-to-moment contribution to astroglial physiology. We thus here investigated the early structural and functional alterations induced in astrocytes by a transient metabolic challenge consisting in glucose deprivation. Electrophysiological recordings of hippocampal astroglial cells of the stratum radiatum in situ revealed that shortage of glucose specifically increases astrocyte membrane capacitance, whilst it has no impact on other passive membrane properties. Consistent with this change, morphometric analysis unraveled a prompt increase in astrocyte volume upon glucose deprivation. Furthermore, characteristic functional properties of astrocytes are also affected by transient glucose deficiency. We indeed found that glucoprivation decreases their gap junction-mediated coupling, while it progressively and reversibly increases their intracellular calcium levels during the slow depression of synaptic transmission occurring simultaneously, as assessed by dual electrophysiological and calcium imaging recordings. Together, these data indicate that astrocytes rapidly respond to metabolic dysfunctions, and are therefore central to the neuroglial dialog at play in brain adaptation to glycopenia.

No MeSH data available.


Related in: MedlinePlus