REM Sleep Loss-Induced Elevated Noradrenaline Plays a Significant Role in Neurodegeneration: Synthesis of Findings to Propose a Possible Mechanism of Action from Molecule to Patho-Physiological Changes.

Wear and tear are natural processes for all living and non-living bodies. All living cells and organisms are metabolically active to generate energy for their routine needs, including for survival. In the process, the cells are exposed to oxidative load, metabolic waste, and bye-products. In an organ, the living non-neuronal cells divide and replenish the lost or damaged cells; however, as neuronal cells normally do not divide, they need special feature(s) for their protection, survival, and sustenance for normal functioning of the brain. The neurons grow and branch as axons and dendrites, which contribute to the formation of synapses with near and far neurons, the basic scaffold for complex brain functions. It is necessary that one or more basic and instinct physiological process(es) (functions) is likely to contribute to the protection of the neurons and maintenance of the synapses. It is known that rapid eye movement sleep (REMS), an autonomic instinct behavior, maintains brain functioning including learning and memory and its loss causes dysfunctions. In this review we correlate the role of REMS and its loss in synaptogenesis, memory consolidation, and neuronal degeneration. Further, as a mechanism of action, we will show that REMS maintains noradrenaline (NA) at a low level, which protects neurons from oxidative damage and maintains neuronal growth and synaptogenesis. However, upon REMS loss, the level of NA increases, which withdraws protection and causes apoptosis and loss of synapses and neurons. We propose that the latter possibly causes REMS loss associated neurodegenerative diseases and associated symptoms.

Rapid eye movement sleep deprivation impairs neuronal plasticity and reduces hippocampal neuronal arborization in male albino rats: Noradrenaline is involved in the process.

Rapid eye movement sleep (REMS) favors brain development and memory, while it is decreased in neurodegenerative diseases. REMS deprivation (REMSD) affects several physiological processes including memory consolidation; however, its detailed mechanism(s) of action was unknown. REMS reduces, while REMSD elevates noradrenaline (NA) level in the brain; the latter induces several deficiencies and disorders, including changes in neuronal cytomorphology and apoptosis. Therefore, we proposed that REMS- and REMSD-associated modulation of NA level might affect neuronal plasticity and affect brain functions. Male albino rats were REMS deprived by flower-pot method for 6 days, and its effects were compared with home cage and large platform controls as well as post-REMSD recovered and REMS-deprived prazosin (α1-adrenoceptor antagonist)-treated rats. We observed that REMSD reduced CA1 and CA3 neuronal dendritic length, branching, arborization, and spine density, while length of active zone and expressions of pre- as well as post-synaptic proteins were increased as compared to controls; interestingly, prazosin prevented most of the effects in vivo. Studies on primary culture of neurons from chick embryo brain confirmed that NA at lower concentration(s) induced neuronal branching and arborization, while higher doses were destructive. The findings support our contention that REMSD adversely affects neuronal plasticity, branching, and synaptic scaffold, which explain the underlying cytoarchitectural basis of REMSD-associated patho-physio-behavioral changes. Consolidation of findings of this study along with that of our previous reports suggest that the neuronal disintegration could be due to either withdrawal of direct protective and proliferative role of low dose of NA or indirect effect of high dose of NA or both.

REM sleep loss-induced elevated noradrenaline could predispose an individual to psychosomatic disorders: a review focused on proposal for prediction, prevention, and personalized treatment.

Historically and traditionally, it is known that sleep helps in maintaining healthy living. Its duration varies not only among individuals but also in the same individual depending on circumstances, suggesting it is a dynamic and personalized physiological process. It has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS). The former is unique that adult humans spend the least time in this stage, when although one is physically asleep, the brain behaves as if awake, the dream state. As NREMS is a pre-requisite for appearance of REMS, the latter can be considered a predictive readout of sleep quality and health. It plays a protective role against oxidative, stressful, and psychopathological insults. Several modern lifestyle activities compromise quality and quantity of sleep (including REMS) affecting fundamental physiological and psychopathosomatic processes in a personalized manner. REMS loss-induced elevated brain noradrenaline (NA) causes many associated symptoms, which are ameliorated by preventing NA action. Therefore, we propose that awareness about personalized sleep hygiene (including REMS) and maintaining optimum brain NA level should be of paramount significance for leading physical and mental well-being as well as healthy living. As sleep is a dynamic, multifactorial, homeostatically regulated process, for healthy living, we recommend addressing and treating sleep dysfunctions in a personalized manner by the health professionals, caregivers, family, and other supporting members in the society. We also recommend that maintaining sleep profile, optimum level of NA, and/or prevention of elevation of NA or its action in the brain must be seriously considered for ameliorating lifestyle and REMS disturbance-associated dysfunctions.