New insights into the “Glycogenetic” hypothesis of sleep: brain glycogen availability affects REM-related theta rhythm providing a possible link with emotional memory mechanisms

S. Burlet-Godinot, J.-M. Petit, P.J. Roach, A.A. Depaoli-Roach, Pierre J. Magistretti

Research output: Contribution to journalArticlepeer-review

Abstract

Since the 1990's, our concept of cerebral glycogen role changed from a passive glucose reserve to a highly dynamically regulated energy buffer involved in neurophysiological functions such as emotional memory formation and/or consolidation. Glycogen synthesis is regulated by glycogen synthase (GYS) that is positively controlled by protein targeting to glycogen (PTG) expression levels whereas its degradation is regulated by glycogen phosphorylase (GYP). In 1995, Bennington and Heller hypothesized that the replenishment of glycogen used during wakefulness, might constitute a main function of sleep. We previously tested this hypothesis and showed that PTG mRNA expression and GYS activity increased in the brain of mice that underwent a 6-hour sleep deprivation while glycogen levels were paradoxically not affected. Therefore, we proposed the “glycogenetic” hypothesis as an alternative hypothesis in which the prevention of glycogen breakdown during wakefulness might create optimal energetic conditions for sleep triggering and maintenance. To test this hypothesis in mice, we analyzed the sleep parameters in a pharmacological model in which glycogen utilization is blocked by a GYP inhibitor (1,4-dioxy-1,4-imino-D-arabinitol (DAB)), and in a genetic model in which the gene encoding PTG was knocked-down, leading to a brain glycogen level reduction of 80%.
Original languageEnglish (US)
Pages (from-to)S300
JournalSleep Medicine
Volume64
DOIs
StatePublished - Dec 2019

ASJC Scopus subject areas

  • Medicine(all)

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