Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in hamster brain

Abstract

Deletion of the core clock gene, Bmal1, ablates circadian rhythms and accelerates aging, leading to cognitive deficits and tissue atrophy (e.g., skeletal muscle) (Kondratov et al., 2006, Kondratova et al, 2010). Although normal aging has been shown to attenuate Bmal1 expression in the master circadian pacemaker in the suprachiasmatic nucleus (SCN), relatively little is known about age-related changes in Bmal1 expression in other tissues, where Bmal1 may have multiple functions. This study tested the hypothesis that aging reduces Bmal1 expression in extra-SCN oscillators including brain substrates for memory and in skeletal muscle. Brains and gastrocnemius muscles were collected from young (3–5 months) and old hamsters (17–21 months) euthanized at four times of day. Bmal1 mRNA expression was determined by conducting in situ hybridization on brain sections or real-time PCR on muscle samples. The results showed age-related attenuation of Bmal1 expression in many brain regions, and included loss of diurnal rhythms in the hippocampal CA2 and CA3 subfields, but no change in muscle. In situ hybridization for Per2 mRNA was also conducted and showed age-related reduction of diurnal rhythm amplitude selectively in the hippocampal CA1 and DG subfields. In conclusion, aging has tissue-dependent effects on Bmal1 expression in extra-SCN oscillators. These finding on normal aging will provide a reference for comparing potential changes in Bmal1 and Per2 expression in age-related pathologies. In conjunction with previous reports, the results suggest the possibility that attenuation of clock gene expression in some brain regions (the hippocampus, cingulate cortex and SCN) may contribute to age-related cognitive deficits.

Abnormal Clock Gene Expression and Locomotor Activity Rhythms in Two Month-Old Female APPSwe/PS1dE9 Mice

“…While these rhythms are altered with normal ageing in several species including mice, hamsters and rats (29)(30)(31), few studies have investigated whether these expression patterns are altered in genetic mouse models relevant to AD. Duncan and colleagues (32) showed the clock gene Per2 is increased at night in the SCN of wild-type mice with a strong trend towards attenuation of this increase in APPxPS1 mice that did not reach statistical significance.…”

The primate seahorse rhythm

“…structures such as the septum that influence hippocampal function (Morin et al, 1994;Ruby et al, 2008Ruby et al, , 2013Watts et al, 1987) and could thus indirectly regulate the rhythmic expression of some proteins in the hippocampus (Duncan et al, 2013;Ikeno et al, 2013;Otalora et al, 2013).…”

“…Furthermore, functions such as processing and learning in the hippocampal memory have been described as important to integrate the circadian information of independent oscillators (Garren et al, 2013;Maury and Queinnec, 1992;Nesca and Koulack, 1994;Smarr et al, 2014). Some of these models have shown evidence of the rhythmic expression of clock genes in the hippocampus (Duncan et al, 2013;Lamont et al, 2005;Otalora et al, 2013;Verwey et al, 2007). In rodents was demonstrated rhythms in Per2 expression in light/dark (LD) or constant darkness (DD) cycles and that these rhythms are autonomous as they are present in isolated hippocampal slices maintained in culture (Wang et al, 2009).…”

“…The integrated rhythmic SCN activity works as a pacemaker for the circadian clocks of non-SCN cells, each of which also rhythmically express clock genes (Duncan et al, 2013). This is reflected in behaviors such as sleep-wake behavior, body temperature, the regulation of hormone secretion, and the acquisition and processing of memory (Chaudhury and Colwell, 2002;Gerstner et al, 2009;Nesca and Koulack, 1994;Ruby et al, 2008Ruby et al, , 2013.…”

Computational model for mammalian circadian oscillator: interacting with NAD+/SIRT1 pathway and age-related changes in gene expression of circadian oscillator

“…В частности, при увеличении возраста отмечено снижение экспрессии генов ЦО Bmal1 и Per2 в SCN мыши (Chang, Guarente, 2013). Аналогичные изменения выявлены в SCN и других областях мозга сирийского хомячка (Duncan et al, 2013). Наблюдалось снижение экспрессии генов Bmal1 и Clock в SCN мыши в возрасте 16 мес.…”