​Neurobiology, Neuropharmacology, Biological clock, Melatonin, Sleep
Department: Neurobiology
Faculty: Life Sciences
Tel Aviv University

Prof. Zisapel Nava

Research Activity:

The Biological Clock and Melatonin Receptors- The daily light/dark cycle provides a reliable signal for coordination and seasonal adaptation of thermoregulation, reproduction, development, sleep and mood. The daily rhythm in production of melatonin by the pineal gland reflects the environmental light /dark cycles and thus plays an important role in the time-keeping system. Melatonin has two major biological effects: a) it provokes the changes in the neuroendocrine system needed to adapt the thermoregulatory and reproductive systems to the approaching season. b) It functions in concert with light to hold circadian rhythms in phase with prevailing environmental conditions. Melatonin has been used successfully in humans to treat circadian time based sleep disorders in adults and improve sleep initiation and maintenance in elderly, in whom the melatonin signal has decayed.

Research focus is on :

Cellular effects of melatonin:  Our knowledge of the molecular mechanisms involved is still limited. Melatonin, shown by us and others to inhibit regulated neurosecretion of dopamine from specific brain areas, also and modulates constitutive secretion of proteins from benign and tumor cells. In the brain and prostate cells, these responses strictly depend on the presence of sex steroids. Melatonin effects nuclear exclusion of the androgen receptor. The signal transduction of this pathway is being studied. The effects of melatonin on the intracellular localization and targeting of proteins have important implications in maintaining and optimizing the temporal order in cells and organs. Understanding the biochemical basis of melatonin responses is important in view of the role of this hormone in circadian rhythms, pubertal development, aging, reproductive and thermoregulatory functions and its oncostatic properties.
Effects of melatonin on the human brain: brain imaging and clinical studies in healthy volunteers and insomnia patients:  Sleep, a state marked by lessened consciousness, lessened movement of the skeletal muscles, and slowed-down metabolism, has an essential, restorative function and an important role in memory consolidation. The sleep need is remarkably standardized in quality, quantity and timing. Sleep is an orchestrated neurochemical process involving sleep promoting and arousal centers in the brain. In humans sleep normally occurs during the night. Sleep disturbance results in fatigue and problems staying awake. Exogenous melatonin elicits all the physiological effects that occur in the evening during endogenous melatonin secretion: increases sleep propensity, lowers body temperature and phase shift the biological clock. The production of melatonin declines with aging and in about half of insomnia patients it is lower than normal for their age group. The question of where and how melatonin acts in the brain is of prime importance in our attempts to unravel the neuronal mechanisms underlying sleep regulation, the restorative value of sleep and consequently management of daytime fatigue .

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