Glucose is the main brain fuel in fed conditions, while astrocytic
glycogen is used as supplemental fuel when the brain is stimulated. Brain
glycogen levels are decreased shortly after induced
seizures in rodents, but little is known about how
glycogen levels are affected interictally in chronic models of
epilepsy. Reduced
glutamine synthetase activity has been suggested to lead to increased brain
glycogen levels in humans with chronic
epilepsy. Here, we used the mouse
pilocarpine model of
epilepsy to investigate whether brain
glycogen levels are altered, both acutely and in the chronic stage of the model. One day after
pilocarpine-induced convulsive
status epilepticus (CSE),
glycogen levels were higher in the hippocampal formation, cerebral cortex, and cerebellum. Opposite to expected, this was accompanied by elevated
glutamine synthetase activity in the hippocampus but not the cortex. Increased interictal
glycogen amounts were seen in the hippocampal formation and cerebral cortex in the chronic stage of the model (21 days post-CSE), suggesting long-lasting alterations in
glycogen metabolism.
Glycogen solubility in the cerebral cortex was unaltered in this
epilepsy mouse model.
Glycogen synthase kinase 3 beta (Gsk3b)
mRNA levels were reduced in the hippocampal formations of mice in the chronic stage, which may underlie the elevated brain
glycogen content in this model. This is the first report of elevated interictal
glycogen levels in a chronic
epilepsy model. Increased
glycogen amounts in the brain may influence seizure susceptibility in this model, and this warrants further investigation.