Sleep, plasticity and the pathophysiology of neurodevelopmental disorders: the potential roles of protein synthesis and other cellular processes

Abstract

Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.

Keywords: autism; memory; neurodevelopmental disorders; plasticity; protein synthesis; sleep.

Figure 1

Hypothetical scheme illustrating cellular consequences of sleep deprivation. Prolonged wakefulness leads to the activation of cellular stress events: Endoplasmic reticulum (ER) stress and oxidative stress are activated. Myelination is downregulated. Protein synthesis (in addition to mTORC1 activity) is diminished (both globally and at synapses). Despite these changes, net synaptic upscaling occurs without proper pruning. There is also a possible relationship between the increased number of synapses and decreased neuroligin following sleep deprivation. In addition, accumulation of sleep regulatory substances in the post-synaptic terminal may lead to an increased drive for sleep.