Sleep Deprivation and Neurological Disorders

Abstract

Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin proteins like α-synuclein, amyloid-β, and tau which are involved in major neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. In addition, SD is also shown to affect the glymphatic system, a glial-dependent metabolic waste clearance pathway, causing accumulation of misfolded faulty proteins in synaptic compartments resulting in cognitive decline. Also, SD affects the immunological and redox system resulting in neuroinflammation and oxidative stress. Hence, it is important to understand the molecular and biochemical alterations that are the causative factors leading to these pathophysiological effects on the neuronal system. This review is an attempt in this direction. It provides up-to-date information on the alterations in the key processes, pathways, and proteins that are negatively affected by SD and become reasons for neurological disorders over a prolonged period of time, if left unattended.

Figure 1

(a) Brain structures involved in REM sleep. PPT/LDT initiates firing during REM sleep and helps in switching between NREM and REM sleep. GABAergic neurons in the hypothalamus promote REM sleep by inactivating vlPAG/dDpMe REM-off GABAergic neurons. SLD consists of projections to glycinergic neuron Raphe magnus, ventral and alpha gigantocellular nuclei, lateral paragigantocellular nucleus, and also spinal, facial, trigeminal neurons and thereby produce muscle atonia during REM sleep. (b) Brain structures involved in NREM sleep. Ventrolateral preoptic area and median preoptic nucleus contain GABAergic neurons that release galanin which inhibit cholinergic neurons in regions like locus coeruleus, Basal Forebrain, TMN, and orexin neurons, thereby inhibiting arousal. The basal forebrain consists of GABAergic neurons that inhibit cortical activation and somatostatin inhibits wake active neurons in the basal forebrain. Parafacial zone releases GABA onto parabrachial neurons which in turn release glutamate onto cortically projecting neurons of the BF, hence promoting SWS. Cortical nitric oxide synthase neurons release GABA and promote SWS.

Figure 2

Sleep deprivation-induced alteration in various pathways leading to AD pathology. SD increases neuronal firing, upregulates BACE 1 proteins, and aggravates neuroinflammation and oxidative stress. Alterations in these pathways impair clearance of the toxic metabolites and leading to the accumulation of Aβ and tau proteins. SD has a negative impact on the cholinergic neurons, and this attributes to cognitive dysfunction and impaired memory in AD patients.

Figure 3

Sleep is a vital phenomenon and an indicator of overall health. Normal sleep is very essential for memory and brain health since various neural circuits in the brain are involved in sleep. Sleep deprivation has evolved as a major threat in modern society. SD impairs LTP and molecules associated with memory and leads to cognitive dysfunction. SD also impairs the clearance of toxic metabolites produced in the brain and contributes to the pathophysiology of neurological disorders like AD, PD, and cerebral stroke. SD also causes an imbalance in the immune system and aggravates the pathophysiology of MS and glioma. It can be concluded that SD adversely affects various proteins, genes, and molecular cascades in neurodegenerative disorders.