Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats

Abstract

Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. In this experiment, we examined clock gene expression to determine whether circadian input, oscillation, and output are disrupted with aging. Circadian expression profiles of rPer1, rPer2, or rCry1 mRNA were very similar in the SCN, the paraventricular nucleus of the hypothalamus (PVN), and the pineal body of young and aged (22-26 months) rats. On the other hand, the photic stimulation-induced rapid expression of Per1 and Per2 in the SCN was reduced with aging. The present results suggest that the molecular mechanism of clock oscillation in the SCN, PVN, and pineal body is preserved against aging, whereas the impairment of Per1 induction in the SCN after light stimulation may result in impaired behavioral photic entrainment in aged rats.

Circadian Rhythms, Sleep, and Disorders of Aging

“…Data are mixed as to whether aging impairs SCN entrainment to light [15,16]. On the other hand, it is clear that peripheral oscillators dampen with age, whether from loss of intrinsic clock function or decline in entraining signals from the SCN, and could contribute to the aging process [17].…”

The Circadian Clock in Cancer Development and Therapy

“…Aging is frequently associated with disruption of circadian rhythmicity in humans and animal models 288–290 . Premature aging is commonly observed among circadian gene-mutant mouse models.…”

Plastic oscillators and fixed rhythms: Changes in the phase of clock-gene rhythms in the PVN are not reflected in the phase of the melatonin rhythm of grass rats

“…The major finding of Experiment 1A was that when a rhythm in PER2 protein expression was present in the PVN of grass rats, it featured a peak late in the light period (i.e., ZT 10), which is about 12 hours earlier than what the mRNA data predict for PER1 in nocturnal species (Asai et al, 2001, Minana-Solis et al, 2009, Dzirbikova et al, 2011). Since PER 1 and 2 appear to have redundant roles in circadian regulation (for example see (Maywood et al, 2014), these results serve to extend previous observations of phase differences in extra-SCN oscillators between grass rats and nocturnal rodents (Ramanathan et al, 2010b) to a hypothalamic nucleus with connections to autonomic neurons (Swanson and Kuypers, 1980, Swanson and Sawchenko, 1980, Swanson et al, 1980,Teclemariam-Mesbah et al, 1999) and to pre-autonomic brain sites (Stern, 2001, Kalsbeek et al, 2011).…”

“…In the hypothalamus of laboratory rats, rhythmic expression of PER mRNA, but not PER2 mRNA or protein, has been described in the paraventricular nucleus (PVN; Asai et al 2001; Minana-Solis et al, 2009). The PVN receives direct inputs from the SCN (Munch et al, 2002) and is part of a multi-synaptic pathway that is responsible for the circadian and photic regulation of the pineal gland and the pineal's melatonin rhythm (Moore, 1996).…”

“…Thus, given the common phase of the melatonin rhythm across diurnal and nocturnal mammalian species and the involvement of the PVN in the mediation of that rhythm, one question addressed here relates to potential differences as well as similarities between the phase of the PVN oscillator in diurnal and nocturnal mammalian species. For nocturnal laboratory rats, mRNA for PER1 peaks around zeitgeber time (ZT) 16 (Asai et al, 2001, Minana-Solis et al, 2009); suggesting that the peak of PER 1 protein occurs during the late night, which is the time of peak PER protein expression in several areas of the brain of nocturnal species (Amir et al, 2004, Lamont et al, 2005, Angeles-Castellanos et al, 2007, Feillet et al, 2008); comparable data for the PVN are not available from diurnal mammalian species.…”