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

Asai, M.; Yoshinobu, Yuko; Kaneko, Satoshi; Mori, Akira; Nikaido, Takato; Moriya, Takuya; Akiyama, Masashi; Shibata, Shigenobu

doi:10.1002/jnr.10010.abs

Cited by 56 publications

(90 citation statements)

References 39 publications

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“…As clock gene oscillation in the SCN was normal in phase II db/db mice, attenuation and arrhythmicity of the locomotor activity and clock gene mRNA rhythm in the liver did not result from a diminishing of the core SCN oscillator but rather from abnormalities stemming from the output mechanism mediating locomotor activity and peripheral clock resetting. Similar results were reported using old animals, in which clock gene expression in the SCN was maintained but locomotor activity was severely diminished [31]. Thus, obesity may be responsible for the reduction of locomotor activity, and hyperphagia may be responsible for the arrhythmicity of locomotor activity in db/db mice.…”

Section: Discussionsupporting

confidence: 84%

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver

et al. 2004

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Aims/hypothesis. An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. Methods. Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. Results. The db/db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. Conclusions/interpretation. We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

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Section: Discussionsupporting

confidence: 84%

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver

et al. 2004

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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: 92%

“…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%

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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“…In aged animals, Per1 expression following an entraining light stimulus is markedly reduced with a significantly longer delay to resynchronization (Davidson et al, 2008;Kolker et al, 2003). In young animals, disruption of the Period genes leads to aging-like declines in sensitivity to light (Asai et al, 2001;Weinert et al, 2001). These findings suggest that temporal disorganization with advancing age may result, in part, from reductions in the sensitivity of the SCN to retinal stimulation.…”

Section: A Aged-related Changes In Circadian Entrainmentmentioning

confidence: 99%

Aging in the circadian system: Considerations for health, disease prevention and longevity

Gibson

Williams

Kriegsfeld

2009

Experimental Gerontology

139

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The circadian system orchestrates internal physiology on a daily schedule to promote optimal health and maximize disease prevention. Chronic disruptions in circadian function are associated with an increase in a variety of disease states including, heart disease, ulcers, and diabetes. With advanced age, the genes regulating circadian function at the cellar level become disorganized and the ability of the brain clock to entrain to local time diminishes. As a result, aged individuals exhibit a loss of temporal coordination among bodily systems, leading to deficits in homeostasis and sub-optimal functioning. Such disruptions in the circadian system appear to accelerate the aging process and contribute to senescence, with some systems being more vulnerable than others. This review explores aging-associated changes in circadian function and examines evidence linking such alterations to adverse health consequences in late life and promotion of the aging process.

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

Cited by 56 publications

References 39 publications

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver

Resetting of central and peripheral circadian oscillators in aged rats

Aging in the circadian system: Considerations for health, disease prevention and longevity

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