Effect of melatonin on age induced changes in daily serotonin rhythms in suprachiasmatic nucleus of male Wistar rat

Abstract

The decline in physiological functions with aging may affect the ability of the SCN, the biological clock, circadian pacemaker to transmit rhythmic information to other neural target sites, and thereby modify the expression of biological rhythms resulting in circadian disorders. Neurotransmitter serotonin plays important role in the photic and non-photic regulation of circadian rhythms and is a precursor of neurohormone melatonin, an internal zeitgeber. To assess effects of aging on the functional integrity of circadian system, we studied daily serotonin rhythms in the SCN by measuring serotonin levels at variable time points in wide range of age groups such as 15 days, 1, 2, 3 (adult), 4, 6, 9, 12, 18 and 24 months old male wistar rats. Animals were maintained in light-dark conditions (LD; 12:12) two weeks prior to experiment. We report here that in 15 days, 1 and 2 months old rat SCN the mean serotonin level is low and daily serotonin rhythm is just beginning; at 3, 4 and 6 months, serotonin levels and rhythms are robust and at 9, 12, 18 and 24 months mean serotonin levels are low again and rhythm is becoming more disrupted. Previous studies have shown the 5-HT rhythmicity was established by 3 month in rat brain but disintegrated by 6 months of age. As melatonin, an endogenous synchronizer and an antiaging agent, declines with aging, the effects of exogenous melatonin administration on serotonin rhythmicity in SCN in 3, 6, 9 and 24 months old rats were studied to assess effects of aging on responsiveness to melatonin. Our studies indicated an age related loss of sensitivity to melatonin in the restoration of age induced changes in SCN serotonin amplitude and rhythmicity.

Aging signaling pathways and circadian clock-dependent metabolic derangements

“…In mammals, disruption of circadian rhythms with age might be associated with a reduced sensitivity of SCN to entrainment signals 90, 91 . For example, aged mice are less sensitive to light entrainment than young ones and have reduced Per2 expression 92, 93 , reduced responsiveness to melatonin 94 and serotonin in the SCN 95 .…”

“…For example, aged mice are less sensitive to light entrainment than young ones and have reduced Per2 expression 92, 93 , reduced responsiveness to melatonin 94 and serotonin in the SCN 95 . Clock -/- and Bmal1 -/- mice, on top of impaired glucose homeostasis, exhibit premature age-associated disorders and reduced lifespan 72, 87, 98, 99 , as well as increased sensitivity to genotoxic stress 100 .…”

Melatonin Alters Age-Related Changes in Transcription Factors and Kinase Activation

“…This may account for the lack of habituation to, and absence of, withdrawal effects of melatonin [24] and its analogs [25]. It has been reported the sensitivity to melatonin is reduced with age in the suprachiasmantic nucleus [26]. This may reflect reduction of melatonin receptor density and thus account for the ability of elevated levels of exogenous melatonin to reverse age-related changes in nervous tissue.…”

Nicotinamide adenine dinucleotide: a possible circadian zeitgeber functioning in nontranscription oscillation

“…To keep synchrony with the environment, circadian rhythms need to be entrained daily by means of zeitgeber ("time giver") signals, including light (Golombek & Rosenstein 2010) and many nonphotic zeitgebers (Jagota & Kalyani 2010, Oda & Friesen 2011. This fundamental biological function is involved in many physiological processes, including heart rate (Hu et al 2008), blood pressure (Singh et al 2003), neural activity (Colwell 2011), reproductive processes (Turek 1992), and energy metabolism (Kalsbeek et al 2011).…”