The glycolytic metabolite methylglyoxal induces changes in vigilance by generating low-amplitude non-REM sleep

Abstract

Methylglyoxal (MG), an essential by-product of glycolysis, is a highly reactive endogenous α-oxoaldehyde. Although high levels of MG are cytotoxic, physiological doses of MG were shown to reduce anxiety-related behavior through selective activation of γ-aminobutyric acid type A (GABA_A) receptors. Because the latter play a major role in sleep induction, this study examined the potential of MG to regulate sleep. Specifically, we assessed how MG influences sleep-wake behavior in CD1 mice that received intracerebroventricular injections of either vehicle or 0.7 µmol MG at onset of darkness. We used electroencephalogram (EEG) and electromyogram (EMG) recordings to monitor changes in vigilance states, sleep architecture and the EEG spectrum, for 24 h after receipt of injections. Administration of MG rapidly induced non-rapid eye movement sleep (NREMS) and, concomitantly, decreased wakefulness and suppressed EEG delta power during NREMS. In addition, MG robustly enhanced the amount and number of episodes of an unclassified state of vigilance in which EMG, as well as EEG delta and theta power, were very low. MG did not affect overall rapid eye movement sleep (REMS) in a given 24-h period, but significantly reduced the power of theta activity during REMS. Our results provide the first evidence that MG can exert sleep-promoting properties by triggering low-amplitude NREMS.