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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 deprivation increases astroglial volume. (A) Sample confocal images of an enhanced green fluorescent protein (eGFP) labeled hippocampal astrocyte from a glial fibrillary acidic protein (GFAP)-eGFP mouse illustrated before (Control) and after 30 min of exogenous glucose deprivation. Scale bar, 10 μm. (B) Time-dependent changes in astrocytic total (red circles), soma (green circles) and processes (blue triangles) volumes were quantified using 3D confocal morphometry analysis in each individual cell every 5 min during exogenous glucose deprivation and after 10 min of washout. Volume changes were normalized to values measured at t = 0 and expressed relative to this baseline as an increase in percentage. Glucose deprivation increased significantly all astrocytic volumes, and this effect was partially reversible after 10 min of glucose re-introduction (n = 22 cells, 10 slices, 4 mice). Asterisks indicate statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001).
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Figure 2: Glucose deprivation increases astroglial volume. (A) Sample confocal images of an enhanced green fluorescent protein (eGFP) labeled hippocampal astrocyte from a glial fibrillary acidic protein (GFAP)-eGFP mouse illustrated before (Control) and after 30 min of exogenous glucose deprivation. Scale bar, 10 μm. (B) Time-dependent changes in astrocytic total (red circles), soma (green circles) and processes (blue triangles) volumes were quantified using 3D confocal morphometry analysis in each individual cell every 5 min during exogenous glucose deprivation and after 10 min of washout. Volume changes were normalized to values measured at t = 0 and expressed relative to this baseline as an increase in percentage. Glucose deprivation increased significantly all astrocytic volumes, and this effect was partially reversible after 10 min of glucose re-introduction (n = 22 cells, 10 slices, 4 mice). Asterisks indicate statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001).

Mentions: We found that the total volume of astrocytes increased by ~22% during the 30 min glucose deprivation compared to the volume measured before glucose deficiency (peak increase at t = 30 min of glucose deprivation compared to t = 0: +21.5 ± 5.5%; n = 22; p < 0.001; Figures 2A,B). To determine whether the increase in astrocyte volume was homogenous throughout its domain, we measured the volume changes occurring locally in astrocyte soma and in processes that were induced by glucose deficiency. The volume of astrocyte somas, expressed as a fraction of the total cell volume, only increased by ~14% (+13.9 ± 2.5%, n = 22; p < 0.001), while volume changes in astrocytic processes were more pronounced, reaching ~25% after 30 min of glucose deficiency (+24.5 ± 7.1%; n = 22; p < 0.001; Figure 2B). Noteworthy, in response to glucose deprivation, the total volume of astrocytes displayed a pattern similar to the volume of their processes, consistent with the fact that the latter exceed by far the volume of the soma, and therefore accounts for most of astrocyte total volume. Over the course of glucose deprivation, the increases in astrocyte total and process volume were indeed consistently slightly stronger than the increase in soma volume, although the differences were not statistically significant (p > 0.05; Figure 2B).


Glucose Tightly Controls Morphological and Functional Properties of Astrocytes.

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

Glucose deprivation increases astroglial volume. (A) Sample confocal images of an enhanced green fluorescent protein (eGFP) labeled hippocampal astrocyte from a glial fibrillary acidic protein (GFAP)-eGFP mouse illustrated before (Control) and after 30 min of exogenous glucose deprivation. Scale bar, 10 μm. (B) Time-dependent changes in astrocytic total (red circles), soma (green circles) and processes (blue triangles) volumes were quantified using 3D confocal morphometry analysis in each individual cell every 5 min during exogenous glucose deprivation and after 10 min of washout. Volume changes were normalized to values measured at t = 0 and expressed relative to this baseline as an increase in percentage. Glucose deprivation increased significantly all astrocytic volumes, and this effect was partially reversible after 10 min of glucose re-introduction (n = 22 cells, 10 slices, 4 mice). Asterisks indicate statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Glucose deprivation increases astroglial volume. (A) Sample confocal images of an enhanced green fluorescent protein (eGFP) labeled hippocampal astrocyte from a glial fibrillary acidic protein (GFAP)-eGFP mouse illustrated before (Control) and after 30 min of exogenous glucose deprivation. Scale bar, 10 μm. (B) Time-dependent changes in astrocytic total (red circles), soma (green circles) and processes (blue triangles) volumes were quantified using 3D confocal morphometry analysis in each individual cell every 5 min during exogenous glucose deprivation and after 10 min of washout. Volume changes were normalized to values measured at t = 0 and expressed relative to this baseline as an increase in percentage. Glucose deprivation increased significantly all astrocytic volumes, and this effect was partially reversible after 10 min of glucose re-introduction (n = 22 cells, 10 slices, 4 mice). Asterisks indicate statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001).
Mentions: We found that the total volume of astrocytes increased by ~22% during the 30 min glucose deprivation compared to the volume measured before glucose deficiency (peak increase at t = 30 min of glucose deprivation compared to t = 0: +21.5 ± 5.5%; n = 22; p < 0.001; Figures 2A,B). To determine whether the increase in astrocyte volume was homogenous throughout its domain, we measured the volume changes occurring locally in astrocyte soma and in processes that were induced by glucose deficiency. The volume of astrocyte somas, expressed as a fraction of the total cell volume, only increased by ~14% (+13.9 ± 2.5%, n = 22; p < 0.001), while volume changes in astrocytic processes were more pronounced, reaching ~25% after 30 min of glucose deficiency (+24.5 ± 7.1%; n = 22; p < 0.001; Figure 2B). Noteworthy, in response to glucose deprivation, the total volume of astrocytes displayed a pattern similar to the volume of their processes, consistent with the fact that the latter exceed by far the volume of the soma, and therefore accounts for most of astrocyte total volume. Over the course of glucose deprivation, the increases in astrocyte total and process volume were indeed consistently slightly stronger than the increase in soma volume, although the differences were not statistically significant (p > 0.05; Figure 2B).

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