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

Nov 20, 2012Brain research

Aging’s impact on daily rhythm genes outside the main brain clock in hamsters

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Abstract

Aging leads to a reduction in Bmal1 expression in multiple brain regions, particularly affecting the hippocampus.

Deletion of the Bmal1 gene disrupts circadian rhythms and accelerates aging, resulting in cognitive deficits and tissue atrophy.
Bmal1 expression declines with age in various brain regions associated with memory, while remaining unchanged in skeletal muscle.
Loss of diurnal rhythms in Bmal1 expression was observed specifically in the hippocampal CA2 and CA3 subfields of older hamsters.
Age-related reductions in the amplitude of diurnal rhythms were also found in Per2 expression in the hippocampal CA1 and dentate gyrus.
These findings suggest that reductions in clock gene expression in certain brain areas could be linked to cognitive decline associated with aging.

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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.

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

Abstract

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