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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 intracellular calcium levels in astrocytes. (A) Schematic depicting in a hippocampal slice dual recordings of field excitatory postsynaptic potentials (fEPSPs) evoked by Schaffer collaterals stimulation (Stim) and astroglial calcium levels. (B–C) Sample fluorescence images recorded in the orange zone shown in (A), illustrating calcium levels of stratum radiatum astrocytes detected by Fluo-4 imaging (B), and corresponding fEPSPs traces simultaneously recorded (C) before (Control) and after 30 min of glucose deprivation. Color bar: 0–255 (arbitrary fluorescence units, 8 bits resolution). Scale bars: 10 μm (B) and 0.2 mV, 20 ms (C). (D) Quantification of simultaneous relative changes in astroglial calcium levels (ΔF/F0 in 4 color coded astrocytes, upper panel) and fEPSP slope (white circles, lower panel) induced by glucose deprivation in a representative experiment. Scale bar (upper panel), 2%, 5 min. (E) Cross correlation analysis between the time series of fEPSP and astroglial calcium signals illustrated in (D). The high amplitude of the peak cross correlation coefficient (−0.78 at a time lag of −40 s) indicates a strong correlation between the two signals, where changes in fEPSP precede variations in astroglial calcium levels. (F) Quantification of mean peak relative changes in fEPSP slope and astroglial calcium levels (ΔF/F0) induced by the 30 min glucose deprivation (n = 5 cells, 5 slices, 3 mice). Asterisks indicate statistical significance (***p < 0.001).
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Figure 4: Glucose deprivation increases intracellular calcium levels in astrocytes. (A) Schematic depicting in a hippocampal slice dual recordings of field excitatory postsynaptic potentials (fEPSPs) evoked by Schaffer collaterals stimulation (Stim) and astroglial calcium levels. (B–C) Sample fluorescence images recorded in the orange zone shown in (A), illustrating calcium levels of stratum radiatum astrocytes detected by Fluo-4 imaging (B), and corresponding fEPSPs traces simultaneously recorded (C) before (Control) and after 30 min of glucose deprivation. Color bar: 0–255 (arbitrary fluorescence units, 8 bits resolution). Scale bars: 10 μm (B) and 0.2 mV, 20 ms (C). (D) Quantification of simultaneous relative changes in astroglial calcium levels (ΔF/F0 in 4 color coded astrocytes, upper panel) and fEPSP slope (white circles, lower panel) induced by glucose deprivation in a representative experiment. Scale bar (upper panel), 2%, 5 min. (E) Cross correlation analysis between the time series of fEPSP and astroglial calcium signals illustrated in (D). The high amplitude of the peak cross correlation coefficient (−0.78 at a time lag of −40 s) indicates a strong correlation between the two signals, where changes in fEPSP precede variations in astroglial calcium levels. (F) Quantification of mean peak relative changes in fEPSP slope and astroglial calcium levels (ΔF/F0) induced by the 30 min glucose deprivation (n = 5 cells, 5 slices, 3 mice). Asterisks indicate statistical significance (***p < 0.001).

Mentions: A typical feature of astrocytes, besides passive membrane properties and extensive gap junction coupling, is their calcium signaling, thought to represent their excitability since these cells are electrically silent. Calcium signaling is indeed a characteristic response of astrocytes to local changes in synaptic activity, and can in turn regulate neurotransmission (Khakh and Mccarthy, 2015). We thus here investigated during the course of acute glucose deprivation the synchronous changes occurring in synaptic transmission of hippocampal CA1 pyramidal neurons and in intracellular calcium levels of adjacent astrocytes. To do so, we performed dual recordings of stratum radiatum astroglial calcium levels and fEPSPs evoked by Schaffer collateral stimulation (Figures 4A–C).


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 intracellular calcium levels in astrocytes. (A) Schematic depicting in a hippocampal slice dual recordings of field excitatory postsynaptic potentials (fEPSPs) evoked by Schaffer collaterals stimulation (Stim) and astroglial calcium levels. (B–C) Sample fluorescence images recorded in the orange zone shown in (A), illustrating calcium levels of stratum radiatum astrocytes detected by Fluo-4 imaging (B), and corresponding fEPSPs traces simultaneously recorded (C) before (Control) and after 30 min of glucose deprivation. Color bar: 0–255 (arbitrary fluorescence units, 8 bits resolution). Scale bars: 10 μm (B) and 0.2 mV, 20 ms (C). (D) Quantification of simultaneous relative changes in astroglial calcium levels (ΔF/F0 in 4 color coded astrocytes, upper panel) and fEPSP slope (white circles, lower panel) induced by glucose deprivation in a representative experiment. Scale bar (upper panel), 2%, 5 min. (E) Cross correlation analysis between the time series of fEPSP and astroglial calcium signals illustrated in (D). The high amplitude of the peak cross correlation coefficient (−0.78 at a time lag of −40 s) indicates a strong correlation between the two signals, where changes in fEPSP precede variations in astroglial calcium levels. (F) Quantification of mean peak relative changes in fEPSP slope and astroglial calcium levels (ΔF/F0) induced by the 30 min glucose deprivation (n = 5 cells, 5 slices, 3 mice). Asterisks indicate statistical significance (***p < 0.001).
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Figure 4: Glucose deprivation increases intracellular calcium levels in astrocytes. (A) Schematic depicting in a hippocampal slice dual recordings of field excitatory postsynaptic potentials (fEPSPs) evoked by Schaffer collaterals stimulation (Stim) and astroglial calcium levels. (B–C) Sample fluorescence images recorded in the orange zone shown in (A), illustrating calcium levels of stratum radiatum astrocytes detected by Fluo-4 imaging (B), and corresponding fEPSPs traces simultaneously recorded (C) before (Control) and after 30 min of glucose deprivation. Color bar: 0–255 (arbitrary fluorescence units, 8 bits resolution). Scale bars: 10 μm (B) and 0.2 mV, 20 ms (C). (D) Quantification of simultaneous relative changes in astroglial calcium levels (ΔF/F0 in 4 color coded astrocytes, upper panel) and fEPSP slope (white circles, lower panel) induced by glucose deprivation in a representative experiment. Scale bar (upper panel), 2%, 5 min. (E) Cross correlation analysis between the time series of fEPSP and astroglial calcium signals illustrated in (D). The high amplitude of the peak cross correlation coefficient (−0.78 at a time lag of −40 s) indicates a strong correlation between the two signals, where changes in fEPSP precede variations in astroglial calcium levels. (F) Quantification of mean peak relative changes in fEPSP slope and astroglial calcium levels (ΔF/F0) induced by the 30 min glucose deprivation (n = 5 cells, 5 slices, 3 mice). Asterisks indicate statistical significance (***p < 0.001).
Mentions: A typical feature of astrocytes, besides passive membrane properties and extensive gap junction coupling, is their calcium signaling, thought to represent their excitability since these cells are electrically silent. Calcium signaling is indeed a characteristic response of astrocytes to local changes in synaptic activity, and can in turn regulate neurotransmission (Khakh and Mccarthy, 2015). We thus here investigated during the course of acute glucose deprivation the synchronous changes occurring in synaptic transmission of hippocampal CA1 pyramidal neurons and in intracellular calcium levels of adjacent astrocytes. To do so, we performed dual recordings of stratum radiatum astroglial calcium levels and fEPSPs evoked by Schaffer collateral stimulation (Figures 4A–C).

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