Role of melatonin in physiological mitigation of sleep disruption in an unnatural temporal environment.

Illuminated nights reduce melatonin peak and disrupt sleep. Using this as the basis of the present experimental paradigm, we investigated whether nocturnal melatonin levels were crucial for sleep regulation in a diurnal vertebrate. Acclimated Indian house crows (Corvus splendens) were randomly segregated into three groups of 12 each. For the next 10 days, one group was maintained on 12 L:12 D, as before (LD control); for the other two groups, the absolute darkness was replaced with dim light at night (dLAN; L = ~150 lux, D = ~6 lux). Under dLAN, half an hour before light off time, the LD control and one dLAN group received intraperitoneally 200 μL of vehicle (0.75% physiological saline), while the other dLAN group received a similar 200 μL vehicle but containing melatonin at a dose of 50 μg bird-1 day-1. Under dLAN, exogenous melatonin elevated nocturnal AANAT mRNA and plasma melatonin levels and induced changes in diurnal expressions of clock genes (PER2, CRY1, BMAL1, NPAS2, REVERB) in the pineal gland and hypothalamus, and of genes encoding melatonin receptors (MEL1a, MEL1b) and epigenetic modifiers (HAT1, HDAC2, HDAC4, DNMT3a) in the hypothalamus. Elevated nocturnal melatonin levels bettered sleep with positive effects on the hypothalamic expression of genes associated with nocturnal sleep (cytokine pathway: TLR4, TNFα, IL-1β, NOS1; calcium pathway: CAMK2, SIK3) and awake (ACHM3, EGR1, HOMER1a, OREXIN) states, and with neurogenesis and synaptic plasticity (BDNF, EGR1, CREB). These suggested the role of melatonin in mitigation of the dLAN-induced sleep disruption. Nocturnal melatonin peak levels are a crucial component of the regulatory transcriptional pathways underlying the daily wake-sleep pattern, with far-reaching implications for sleep-related issues in diurnal species including perhaps humans inhabiting an over-lit environment with pervasive light pollution.