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 (GYS1Nestin-KO) mouse to study the functional consequences of glycogen depletion in the brain under hypoxic conditions and susceptibility to epilepsy. GYS1Nestin-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, GYS1Nestin-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.
Highlights
Glycogen is the only storage form of carbohydrate in mammals
To analyze the effects of hypobaric hypoxia on the electrophysiological properties of hippocampal circuits in control and GYS1Nestin−KO mice, spontaneous local field potentials (LFPs) in the hippocampal CA1 area of the animal resting in its home box were recorded at ground level (760 mmHg ≈ 35 m) and under hypobaric conditions (405 mmHg ≈ 5000 m; Figures 1B–E)
We previously described impaired memory formation and synaptic plasticity in GYS1Nestin−KO animals (Duran et al, 2013), thereby confirming that brain glycogen participates in the normal functioning of the brain in physiological conditions and that it plays a key role in memory acquisition and learning
Summary
Glycogen is the only storage form of carbohydrate in mammals. Its concentration in the brain is relatively low compared to that found in the most glycogenic tissues, namely liver and skeletal muscle. Brain glycogen is crucial for neuronal survival and synaptic activity during stress episodes such as hypoglycemia and ischemia (Swanson et al, 1989; Suh et al, 2007), and in euglycemic conditions during periods of increased brain activity (Shulman et al, 2001; Brown et al, 2005). In this regard, regions of high synaptic activity contain greater glycogen stores (Sagar et al, 1987).
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