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Role of brain glycogen in the response to hypoxia and in susceptibility to epilepsy.

López-Ramos JC, Duran J, Gruart A, Guinovart JJ, Delgado-García JM - Front Cell Neurosci (2015)

Bottom Line: Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy.In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3-CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms.We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosciences, Pablo de Olavide University Seville, Spain.

ABSTRACT
Although glycogen is the only carbohydrate reserve of the brain, its overall contribution to brain functions remains unclear. It has been proposed that glycogen participates in the preservation of such functions during hypoxia. Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy. To address these issues, we used our brain-specific Glycogen Synthase knockout (GYS1(Nestin-KO)) mouse to study the functional consequences of glycogen depletion in the brain under hypoxic conditions and susceptibility to epilepsy. GYS1(Nestin-KO) mice presented significantly different power spectra of hippocampal local field potentials (LFPs) than controls under hypoxic conditions. In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3-CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms. Furthermore, GYS1(Nestin-KO) mice showed greater susceptibility to hippocampal seizures and myoclonus following the administration of kainate and/or a brief train stimulation of Schaffer collaterals. We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures.

No MeSH data available.


Related in: MedlinePlus

Spectral analysis of local field potentials (LFPs) recorded in the pyramidal CA1 area from the two groups of mice in different hypobaric situations. (A) Experimental design. Animals were implanted with recording (Rec.) electrodes in the hippocampal CA1 area and with stimulating (St.) electrodes in the ipsilateral Schaffer collateral-commissural pathway. (B,E) From top to bottom are illustrated LFPs recorded and sequenced power spectra (1–5 Hz, 6–10 Hz, 11–20 Hz, and 21–50 Hz) from representative wild-type (WT) and GYS1Nestin-KO (KO) mice placed at ground level (35 m ≈ 760 mmHg) (B), 15 min (C) and 60 min (D) after being placed under hypobaric conditions (5000 m ≈ 405 mmHg), and 24 h after being returned to ground level (760 mmHg; 24 h) (E). Note the different LFP profiles presented by the two groups of mice in the four different hypobaric situations. Calibrations in (E) are also for (B–D). Spectral analysis was averaged from LFPs recorded from n ≥ 10 animals per group. Note the higher spectral powers computed from KO mice in the 6–10 Hz band for the two hypobaric situations when compared with those presented by their littermate controls. Amplitudes of power spectra were normalized taking the sum of the total power spectra (from 1 to 50 Hz) of each animal during the initial 760 mmHg situation as a total power (PWR) of 100. Values are expressed as mean ± SEM. Statistical differences, ∗P < 0.05. Student t-test.
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Figure 1: Spectral analysis of local field potentials (LFPs) recorded in the pyramidal CA1 area from the two groups of mice in different hypobaric situations. (A) Experimental design. Animals were implanted with recording (Rec.) electrodes in the hippocampal CA1 area and with stimulating (St.) electrodes in the ipsilateral Schaffer collateral-commissural pathway. (B,E) From top to bottom are illustrated LFPs recorded and sequenced power spectra (1–5 Hz, 6–10 Hz, 11–20 Hz, and 21–50 Hz) from representative wild-type (WT) and GYS1Nestin-KO (KO) mice placed at ground level (35 m ≈ 760 mmHg) (B), 15 min (C) and 60 min (D) after being placed under hypobaric conditions (5000 m ≈ 405 mmHg), and 24 h after being returned to ground level (760 mmHg; 24 h) (E). Note the different LFP profiles presented by the two groups of mice in the four different hypobaric situations. Calibrations in (E) are also for (B–D). Spectral analysis was averaged from LFPs recorded from n ≥ 10 animals per group. Note the higher spectral powers computed from KO mice in the 6–10 Hz band for the two hypobaric situations when compared with those presented by their littermate controls. Amplitudes of power spectra were normalized taking the sum of the total power spectra (from 1 to 50 Hz) of each animal during the initial 760 mmHg situation as a total power (PWR) of 100. Values are expressed as mean ± SEM. Statistical differences, ∗P < 0.05. Student t-test.

Mentions: Animals were anesthetized with 0.8–3% halothane delivered through a calibrated Fluotec 5 (Fluotec-Ohmeda, Tewksbury, MA, USA) vaporizer at a flow rate of 1–2 L/min oxygen. Following stereotaxic coordinates collected from the Paxinos and Franklin atlas (Paxinos and Franklin, 2001), we implanted bipolar stimulating electrodes in the right Schaffer collateral-commissural pathway of the dorsal hippocampus (2 mm lateral and 1.5 mm posterior to bregma; depth from brain surface, 1.0–1.5 mm) and a recording electrode in the ipsilateral CA1 area (1.2 mm lateral and 2.2 mm posterior to bregma; depth from brain surface, 1.0–1.5 mm). Electrodes were made from 50-μm Teflon-coated tungsten wire (Advent Research Materials Ltd., Eynsham, England). The final location of the recording electrode was determined using as a guide the field potential depth profile evoked by paired (40 ms of interval) pulses presented to the Schaffer collateral pathway. A bare silver wire (0.1 mm) was affixed to the skull as ground. The four wires were connected to a 4-pin socket and the latter was fixed to the skull with the help of two small screws and dental cement. Further details of this chronic preparation have been reported elsewhere (see Figure 1A; Madroñal et al., 2009; Gruart et al., 2012).


Role of brain glycogen in the response to hypoxia and in susceptibility to epilepsy.

López-Ramos JC, Duran J, Gruart A, Guinovart JJ, Delgado-García JM - Front Cell Neurosci (2015)

Spectral analysis of local field potentials (LFPs) recorded in the pyramidal CA1 area from the two groups of mice in different hypobaric situations. (A) Experimental design. Animals were implanted with recording (Rec.) electrodes in the hippocampal CA1 area and with stimulating (St.) electrodes in the ipsilateral Schaffer collateral-commissural pathway. (B,E) From top to bottom are illustrated LFPs recorded and sequenced power spectra (1–5 Hz, 6–10 Hz, 11–20 Hz, and 21–50 Hz) from representative wild-type (WT) and GYS1Nestin-KO (KO) mice placed at ground level (35 m ≈ 760 mmHg) (B), 15 min (C) and 60 min (D) after being placed under hypobaric conditions (5000 m ≈ 405 mmHg), and 24 h after being returned to ground level (760 mmHg; 24 h) (E). Note the different LFP profiles presented by the two groups of mice in the four different hypobaric situations. Calibrations in (E) are also for (B–D). Spectral analysis was averaged from LFPs recorded from n ≥ 10 animals per group. Note the higher spectral powers computed from KO mice in the 6–10 Hz band for the two hypobaric situations when compared with those presented by their littermate controls. Amplitudes of power spectra were normalized taking the sum of the total power spectra (from 1 to 50 Hz) of each animal during the initial 760 mmHg situation as a total power (PWR) of 100. Values are expressed as mean ± SEM. Statistical differences, ∗P < 0.05. Student t-test.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4621300&req=5

Figure 1: Spectral analysis of local field potentials (LFPs) recorded in the pyramidal CA1 area from the two groups of mice in different hypobaric situations. (A) Experimental design. Animals were implanted with recording (Rec.) electrodes in the hippocampal CA1 area and with stimulating (St.) electrodes in the ipsilateral Schaffer collateral-commissural pathway. (B,E) From top to bottom are illustrated LFPs recorded and sequenced power spectra (1–5 Hz, 6–10 Hz, 11–20 Hz, and 21–50 Hz) from representative wild-type (WT) and GYS1Nestin-KO (KO) mice placed at ground level (35 m ≈ 760 mmHg) (B), 15 min (C) and 60 min (D) after being placed under hypobaric conditions (5000 m ≈ 405 mmHg), and 24 h after being returned to ground level (760 mmHg; 24 h) (E). Note the different LFP profiles presented by the two groups of mice in the four different hypobaric situations. Calibrations in (E) are also for (B–D). Spectral analysis was averaged from LFPs recorded from n ≥ 10 animals per group. Note the higher spectral powers computed from KO mice in the 6–10 Hz band for the two hypobaric situations when compared with those presented by their littermate controls. Amplitudes of power spectra were normalized taking the sum of the total power spectra (from 1 to 50 Hz) of each animal during the initial 760 mmHg situation as a total power (PWR) of 100. Values are expressed as mean ± SEM. Statistical differences, ∗P < 0.05. Student t-test.
Mentions: Animals were anesthetized with 0.8–3% halothane delivered through a calibrated Fluotec 5 (Fluotec-Ohmeda, Tewksbury, MA, USA) vaporizer at a flow rate of 1–2 L/min oxygen. Following stereotaxic coordinates collected from the Paxinos and Franklin atlas (Paxinos and Franklin, 2001), we implanted bipolar stimulating electrodes in the right Schaffer collateral-commissural pathway of the dorsal hippocampus (2 mm lateral and 1.5 mm posterior to bregma; depth from brain surface, 1.0–1.5 mm) and a recording electrode in the ipsilateral CA1 area (1.2 mm lateral and 2.2 mm posterior to bregma; depth from brain surface, 1.0–1.5 mm). Electrodes were made from 50-μm Teflon-coated tungsten wire (Advent Research Materials Ltd., Eynsham, England). The final location of the recording electrode was determined using as a guide the field potential depth profile evoked by paired (40 ms of interval) pulses presented to the Schaffer collateral pathway. A bare silver wire (0.1 mm) was affixed to the skull as ground. The four wires were connected to a 4-pin socket and the latter was fixed to the skull with the help of two small screws and dental cement. Further details of this chronic preparation have been reported elsewhere (see Figure 1A; Madroñal et al., 2009; Gruart et al., 2012).

Bottom Line: Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy.In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3-CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms.We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurosciences, Pablo de Olavide University Seville, Spain.

ABSTRACT
Although glycogen is the only carbohydrate reserve of the brain, its overall contribution to brain functions remains unclear. It has been proposed that glycogen participates in the preservation of such functions during hypoxia. Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy. To address these issues, we used our brain-specific Glycogen Synthase knockout (GYS1(Nestin-KO)) mouse to study the functional consequences of glycogen depletion in the brain under hypoxic conditions and susceptibility to epilepsy. GYS1(Nestin-KO) mice presented significantly different power spectra of hippocampal local field potentials (LFPs) than controls under hypoxic conditions. In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3-CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms. Furthermore, GYS1(Nestin-KO) mice showed greater susceptibility to hippocampal seizures and myoclonus following the administration of kainate and/or a brief train stimulation of Schaffer collaterals. We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures.

No MeSH data available.


Related in: MedlinePlus