Aging Alters Circadian and Light-Induced Expression of Clock Genes in Golden Hamsters

Kolker, Daniel E.; Fukuyama, H.; Huang, David S.; Takahashi, Joseph S.; Horton, Teresa H.; Turek, Fred W.

doi:10.1177/0748730403251802

Cited by 144 publications

(118 citation statements)

References 46 publications

(59 reference statements)

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“…Thus, the age-related attenuation of photic induction of phase shifts and SCN Per mRNA expression that has been previously reported in hamsters (Kolker et al, 2003;Zhang et al, 1996) apparently is not mediated by decreased calbindin mRNA expression in the SCN. Furthermore, the present findings in the hamster brain are consistent with previous studies in rats indicating that ageassociated changes in calbindin mRNA occur only in discrete regions.…”

Section: Discussionsupporting

confidence: 58%

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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Aging affects several processes modulated by the 5-HT 7 receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT 7 receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT 7 receptors, we investigated aging modulation of 5-HT 7 receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT 7 receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT 7 receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT 7 receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT 7 receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT 7 receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT 7 receptors and calbindin mRNAs within the same regions suggests that proteins they encode may interact to modulate processes such as circadian timekeeping.

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Section: Discussionsupporting

confidence: 58%

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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“…Molecular work within the SCN has indicated that aging significantly reduces photic induction of c-fos mRNA or FOS protein in mice, rats and hamsters (Zhang et al 1996). In addition, photic activation of cyclic-AMP response element binding protein (CREB) and induction of Per1 within the SCN are both reduced with age in hamsters (Zhang et al 1996;Kolker et al 2003). Our work suggests that these molecular changes seen in response to photic stimuli with age may be due to altered action of glutamate at the NMDA receptor during senescence.…”

Section: Discussionmentioning

confidence: 99%

Circadian clock resetting in the mouse changes with age

Biello

2009

AGE

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The most widely recognised consequence of normal age-related changes in biological timing is the sleep disruption that appears in old age and diminishes the quality of life. These sleep disorders are part of the normal ageing process and consist primarily of increased amounts of wakefulness and reduced amounts of deep sleep. Changes in the amplitude and timing of the sleep-wake cycle appear to represent, at least in part, a loss of effective circadian regulation of sleep. Understanding alterations in the characteristics of stimuli that help to consolidate internal rhythms will lead to recommendations to improve synchronisation in old age. Converging evidence from both human and animal studies indicate that senescence is associated with alterations in the neural structure thought to be primarily responsible for the generation of the circadian oscillation, the suprachiasmatic nuclei (SCN). Work has shown that there are changes in the anatomy, physiology and ability of the clock to reset in response to stimuli with age. Therefore it is possible that at least some of the observed age-related changes in sleep and circadian timing could be mediated at the level of the SCN. The SCN contain a circadian clock whose activity can be recorded in vitro for several days. We have tested the response of the circadian clock to a number of neurochemicals that reset the clock in a manner similar to light, including glutamate, N-methyl-D-aspartate (NMDA), gastrin-releasing peptide (GRP) and histamine (HA). In addition, we have also tested agents which phase shift in a pattern similar to behavioural 'non-photic' signals, including neuropeptide Y (NPY), serotonin (5HT) and gamma-aminobutyric acid (GABA). These were tested on the circadian clock in young and older mice (approximately 4 and 15 months old). We found deficits in the response to specific neurochemicals but not to others in our older mice. These results indicate that some changes seen in the responsiveness of the circadian clock to light with age may be mediated at the level of the SCN. Further, the responsiveness of the circadian clock with age is attenuated to some, but not all stimuli. This suggests that not all clock stimuli loose their effectiveness with age, and that it may be possible to compensate for deficits in clock performance by enhancing the strength of those stimulus pathways which are intact.

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“…Three recent studies have begun to address whether there are changes in molecular rhythm generation in aged animals. In all three studies Period 1 (Per1) and/or Period 2 (Per2) gene expression rhythms were unaffected in the aged SCN [3,19,37]. However, Kolker and colleagues [19] reported that both Bmal1 and Clock expression in the SCN was reduced in aged hamsters.…”

Section: Introductionmentioning

confidence: 90%

“…In all three studies Period 1 (Per1) and/or Period 2 (Per2) gene expression rhythms were unaffected in the aged SCN [3,19,37]. However, Kolker and colleagues [19] reported that both Bmal1 and Clock expression in the SCN was reduced in aged hamsters. Furthermore induction of Per1 in the SCN by a light pulse was also diminished in aged hamsters [19] and rats [3].…”

Section: Introductionmentioning

confidence: 90%

“…However, Kolker and colleagues [19] reported that both Bmal1 and Clock expression in the SCN was reduced in aged hamsters. Furthermore induction of Per1 in the SCN by a light pulse was also diminished in aged hamsters [19] and rats [3]. Yamazaki et al [37] investigated rhythmicity in areas outside the SCN in rats using Per1-luciferase reporter gene technology.…”

Section: Introductionmentioning

confidence: 99%

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Resetting of central and peripheral circadian oscillators in aged rats

Davidson

Yamazaki

Arble

et al. 2008

Neurobiology of Aging

115

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The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6 hr advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase-resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8 month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.

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Aging Alters Circadian and Light-Induced Expression of Clock Genes in Golden Hamsters

Cited by 144 publications

References 46 publications

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Circadian clock resetting in the mouse changes with age

Resetting of central and peripheral circadian oscillators in aged rats

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