Search

Individuals with neurodevelopmental disorders experience persistent sleep deficits, and there is increasing evidence that sleep dysregulation is an underlying cause, rather than merely an effect, of the synaptic and behavioral defects observed in these disorders. At the molecular level, dysregulation of the synaptic proteome is a common feature of neurodevelopmental disorders, though the mechanism connecting these molecular and behavioral phenotypes is an ongoing area of investigation. A role for eIF2α in shifting the local proteome in response to changes in the conditions at the synapse has emerged. Here, we discuss recent progress in characterizing the intersection of local synaptic translation and sleep and propose a reciprocal mechanism of dysregulation in the development of synaptic plasticity defects in neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Sleep is an essential and evolutionarily conserved process that affects many biological functions that are also strongly regulated by cellular metabolism. The interdependence between sleep homeostasis and redox metabolism, in particular, is such that sleep deprivation causes redox metabolic imbalances in the form of over-production of ROS. Likewise (and vice versa), accumulation of ROS leads to greater sleep pressure. Thus, it is theorized that one of the functions of sleep is to act as the brain's "antioxidant" at night by clearing oxidation built up from daily stress of the active day phase. In this review, we will highlight evidence linking sleep homeostasis and regulation to redox metabolism by discussing (1) the bipartite role that sleep–wake neuropeptides and hormones have in redox metabolism through comparing cross-species cellular and molecular mechanisms, (2) the evolutionarily metabolic changes that accompanied the development of sleep loss in cavefish, and finally, (3) some of the challenges of uncovering the cellular mechanism underpinning how ROS accumulation builds sleep pressure and cellularly, how this pressure is cleared. [ABSTRACT FROM AUTHOR]