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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 alters astrocyte membrane capacitance. (A) Representative traces of current-voltage relationships (IV curves) are illustrated before (0 min) and after 30 min of perfusion (30 min) with control (black traces) or 0 glucose artificial cerebrospinal fluid (ACSF; red traces). Scale bar, 2 nA, 50 ms. Mean current-voltage relationships (IV curves) recorded over 30 min are mostly unaltered by shortage of glucose (n = 8 cells, 8 slices, 4 mice) compared to control conditions (n = 7 cells, 7 slices, 5 mice, p > 0.05). (B–D) Both input resistance (Ri) and membrane potential (Vm) were indeed found to be unchanged (n = 8 cells, 8 slices, 4 mice) as compared to the control group perfused with glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.05). The only specific change in the astrocyte membrane properties during the course of glucose deprivation regards cell capacitance, which markedly increased in astrocytes exposed to glucose free (0 glucose, n = 8 cells, 8 slices, 4 mice) ACSF and not in control astrocytes exposed to regular glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.01). Asterisks indicate statistical significance (***p < 0.01).
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Figure 1: Glucose deprivation alters astrocyte membrane capacitance. (A) Representative traces of current-voltage relationships (IV curves) are illustrated before (0 min) and after 30 min of perfusion (30 min) with control (black traces) or 0 glucose artificial cerebrospinal fluid (ACSF; red traces). Scale bar, 2 nA, 50 ms. Mean current-voltage relationships (IV curves) recorded over 30 min are mostly unaltered by shortage of glucose (n = 8 cells, 8 slices, 4 mice) compared to control conditions (n = 7 cells, 7 slices, 5 mice, p > 0.05). (B–D) Both input resistance (Ri) and membrane potential (Vm) were indeed found to be unchanged (n = 8 cells, 8 slices, 4 mice) as compared to the control group perfused with glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.05). The only specific change in the astrocyte membrane properties during the course of glucose deprivation regards cell capacitance, which markedly increased in astrocytes exposed to glucose free (0 glucose, n = 8 cells, 8 slices, 4 mice) ACSF and not in control astrocytes exposed to regular glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.01). Asterisks indicate statistical significance (***p < 0.01).

Mentions: To get insights into the consequences of energy deprivation on astroglial function, we first investigated whether glucose deprivation alters intrinsic electrophysiological properties of astrocytes. We recorded the typical passive membrane properties of astrocytes every 5 min for 30 min of glucose deprivation or regular ACSF (control) by analyzing the current or voltage responses to hyperpolarizing and depolarizing square pulses (I/V relationship illustrated in Figure 1A). We found no alteration in passive whole-cell current patterns (linear I/V relationship) during the course of glucose deprivation compared to the control group (control; n = 7; 0 glucose, n = 8; p > 0.05; Figure 1A). We also found no difference in the astrocyte resting membrane potential (Vm: control: −86.1 ± 6.0 mV, n = 7; 0 glucose: −86.3 ± 3.7 mV, n = 8 at 30 min; p > 0.05; Figure 1B) and input resistance (Ri: control: 24.6 ± 2.6 MΩ, n = 7; 0 glucose: 22.7 ± 3.9 MΩ, n = 8 at 30 min; p > 0.05; Figure 1C) compared to the control group. However, the capacitance specifically increased by more than 2.5 fold in astrocytes exposed to free glucose ACSF (Cm, at t = 0: 15.8 ± 2.0 nF; t = 30 min: 41.5 ± 11.8 nF, n = 8; p < 0.001), while it remained unchanged after 30 min in control cells (Cm, at t = 0: 15.2 ± 4.2 nF; t = 30 min: 14.0 ± 3.7 nF, n = 7; p > 0.05; Figure 1D). As the capacitance is classically considered to reflect cell volume, these data suggest that astroglial volume rapidly increases upon glucose deprivation.


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 alters astrocyte membrane capacitance. (A) Representative traces of current-voltage relationships (IV curves) are illustrated before (0 min) and after 30 min of perfusion (30 min) with control (black traces) or 0 glucose artificial cerebrospinal fluid (ACSF; red traces). Scale bar, 2 nA, 50 ms. Mean current-voltage relationships (IV curves) recorded over 30 min are mostly unaltered by shortage of glucose (n = 8 cells, 8 slices, 4 mice) compared to control conditions (n = 7 cells, 7 slices, 5 mice, p > 0.05). (B–D) Both input resistance (Ri) and membrane potential (Vm) were indeed found to be unchanged (n = 8 cells, 8 slices, 4 mice) as compared to the control group perfused with glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.05). The only specific change in the astrocyte membrane properties during the course of glucose deprivation regards cell capacitance, which markedly increased in astrocytes exposed to glucose free (0 glucose, n = 8 cells, 8 slices, 4 mice) ACSF and not in control astrocytes exposed to regular glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.01). Asterisks indicate statistical significance (***p < 0.01).
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Related In: Results  -  Collection

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Figure 1: Glucose deprivation alters astrocyte membrane capacitance. (A) Representative traces of current-voltage relationships (IV curves) are illustrated before (0 min) and after 30 min of perfusion (30 min) with control (black traces) or 0 glucose artificial cerebrospinal fluid (ACSF; red traces). Scale bar, 2 nA, 50 ms. Mean current-voltage relationships (IV curves) recorded over 30 min are mostly unaltered by shortage of glucose (n = 8 cells, 8 slices, 4 mice) compared to control conditions (n = 7 cells, 7 slices, 5 mice, p > 0.05). (B–D) Both input resistance (Ri) and membrane potential (Vm) were indeed found to be unchanged (n = 8 cells, 8 slices, 4 mice) as compared to the control group perfused with glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.05). The only specific change in the astrocyte membrane properties during the course of glucose deprivation regards cell capacitance, which markedly increased in astrocytes exposed to glucose free (0 glucose, n = 8 cells, 8 slices, 4 mice) ACSF and not in control astrocytes exposed to regular glucose containing ACSF (n = 7 cells, 7 slices, 5 mice, p < 0.01). Asterisks indicate statistical significance (***p < 0.01).
Mentions: To get insights into the consequences of energy deprivation on astroglial function, we first investigated whether glucose deprivation alters intrinsic electrophysiological properties of astrocytes. We recorded the typical passive membrane properties of astrocytes every 5 min for 30 min of glucose deprivation or regular ACSF (control) by analyzing the current or voltage responses to hyperpolarizing and depolarizing square pulses (I/V relationship illustrated in Figure 1A). We found no alteration in passive whole-cell current patterns (linear I/V relationship) during the course of glucose deprivation compared to the control group (control; n = 7; 0 glucose, n = 8; p > 0.05; Figure 1A). We also found no difference in the astrocyte resting membrane potential (Vm: control: −86.1 ± 6.0 mV, n = 7; 0 glucose: −86.3 ± 3.7 mV, n = 8 at 30 min; p > 0.05; Figure 1B) and input resistance (Ri: control: 24.6 ± 2.6 MΩ, n = 7; 0 glucose: 22.7 ± 3.9 MΩ, n = 8 at 30 min; p > 0.05; Figure 1C) compared to the control group. However, the capacitance specifically increased by more than 2.5 fold in astrocytes exposed to free glucose ACSF (Cm, at t = 0: 15.8 ± 2.0 nF; t = 30 min: 41.5 ± 11.8 nF, n = 8; p < 0.001), while it remained unchanged after 30 min in control cells (Cm, at t = 0: 15.2 ± 4.2 nF; t = 30 min: 14.0 ± 3.7 nF, n = 7; p > 0.05; Figure 1D). As the capacitance is classically considered to reflect cell volume, these data suggest that astroglial volume rapidly increases upon glucose deprivation.

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