Neurobehavioural complications of sleep deprivation: Shedding light on the emerging role of neuroactive steroids

Abstract

Sleep deprivation (SD) is associated with a broad spectrum of cognitive and behavioural complications, including emotional lability and enhanced stress reactivity, as well as deficits in executive functions, decision making and impulse control. These impairments, which have profound negative consequences on the health and productivity of many individuals, reflect alterations of the prefrontal cortex (PFC) and its connectivity with subcortical regions. However, the molecular underpinnings of these alterations remain elusive. Our group and others have begun examining how the neurobehavioural outcomes of SD may be influenced by neuroactive steroids, a family of molecules deeply implicated in sleep regulation and the stress response. These studies have revealed that, similar to other stressors, acute SD leads to increased synthesis of the neurosteroid allopregnanolone in the PFC. Whereas this up‐regulation is likely aimed at counterbalancing the detrimental impact of oxidative stress induced by SD, the increase in prefrontal allopregnanolone levels contributes to deficits in sensorimotor gating and impulse control, signalling a functional impairment of PFC. This scenario suggests that the synthesis of neuroactive steroids during acute SD may be enacted as a neuroprotective response in the PFC; however, such compensation may in turn set off neurobehavioural complications by interfering with the corticolimbic connections responsible for executive functions and emotional regulation.

Effect of the anodal transcranial direct current electrical stimulation on cognition of medical residents with acute sleep deprivation

“…Long working hours and high cognitive demand may lead to acute and chronic sleep deprivation in professional guards, drivers, military personnel, and healthcare workers, among others. Sleep deprivation increases response time to stimuli and lowers precision, as well as causing inattention, emotional lability, somnolence, and chronic fatigue 1 . A previous study has shown that a state of acute sleep deprivation (17-19 hours) has an equivalent effect as a serum level of 0.05% of alcohol and the response speeds were up to 50% slower for some cognitive tests and accuracy measures considered in many countries as incompatible with safe driving 2 .…”

Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions

“…The study shows potential mechanisms that underlie sex-related differences in behavior and its implications for stress-related illnesses. [199] Animal and human studies [210]…”

Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage

“…Neuroactive steroids (neurosteroids) are compounds synthesized de novo in neurons that modulate both gene expression and neuronal excitability, the latter through interactions with neurotransmitter receptors (for review, see Porcu et al, 2016 ; Paul et al, 2020 ). Neurosteroid levels in serum and brain are dysregulated in multiple psychiatric disorders (e.g., Rapkin et al, 1997 ; Brambilla et al, 2003 ; Hellgren et al, 2014 ; Frau et al, 2020 ; Hantsoo and Epperson, 2020 ). Moreover, allopregnanolone, a metabolite of progesterone and a GABAergic neurosteroid, has emerged as a clinically beneficial therapeutic ( Milivojevic et al, 2016 ; Bixo et al, 2017 ; Meltzer-Brody et al, 2018 ).…”