<i>Bmal1</i>in the Nervous System Is Essential for Normal Adaptation of Circadian Locomotor Activity and Food Intake to Periodic Feeding

Mieda, Michihiro; Sakurai, Takeshi

doi:10.1523/jneurosci.2801-11.2011

Cited by 54 publications

(54 citation statements)

References 24 publications

(34 reference statements)

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“…These mice do not display gross peripheral pathologies. Similar mice were previously reported to have partially intact Bmal1 expression in the SCN, rescuing the circadian regulation of locomotor activity and sleep (32). Locomotor circadian rhythms were largely retained in our NestinCre + ;Bmal1 f/f mice as compared with mice lacking Cre, with no genotype difference in the free-running period, although there was a trend toward a slightly shorter free-running period, similar to that reported previously (ref.…”

Section: Oscillation Of Circadian Clock Genes Is Controlled By Bmal1 supporting

confidence: 89%

“…Locomotor circadian rhythms were largely retained in our NestinCre + ;Bmal1 f/f mice as compared with mice lacking Cre, with no genotype difference in the free-running period, although there was a trend toward a slightly shorter free-running period, similar to that reported previously (ref. 32, Figure 3, A-C, and Supplemental Figure 4A). Using EEG, we saw that grossly normal sleep-wake oscillation was retained in NestinCre + ; Bmal1 f/f mice in 12-hour light/12-hour dark housing conditions (Supplemental Figure 4, B and C).…”

Section: Oscillation Of Circadian Clock Genes Is Controlled By Bmal1 mentioning

confidence: 95%

See 1 more Smart Citation

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Musiek¹,

Lim²,

Yang³

et al. 2013

J. Clin. Invest.

415

448

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Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator-like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration.

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Section: Oscillation Of Circadian Clock Genes Is Controlled By Bmal1 supporting

confidence: 89%

Section: Oscillation Of Circadian Clock Genes Is Controlled By Bmal1 mentioning

confidence: 95%

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Musiek¹,

Lim²,

Yang³

et al. 2013

J. Clin. Invest.

415

448

View full text Add to dashboard Cite

show abstract

“…It is particularly noteworthy that the product of Arntl ( Bmal1 ) is a transcription factor that is a core component of the mammalian circadian rhythm system (Buhr and Takahashi 2013). Studies with knockout mice indicate that Bmal1 plays an important role in the entrainment of locomotor activity that occurs when animals are put on a restricted feeding schedule (Mieda and Sakurai 2011; Zhang et al 2012). The DID paradigm is reminiscent of the restricted feeding protocol, in that alcohol is available only during a restricted period.…”

Section: Discussionmentioning

confidence: 99%

“…However, Bmal1 expression was lower in brains of the LXS mice that showed higher alcohol consumption in the DID model (Table 3). The lower Bmal1 expression would be expected to result in lower locomotor activity in these mice during the period of restricted access to alcohol (Mieda and Sakurai 2011). Since our candidate gene results are based on whole brain transcriptional analyses, it is important to note that Bmal1 expression in regions of the brain outside of the suprachiasmatic nucleus were implicated in the adaptation to food restriction (Mieda and Sakurai 2011).…”

Section: Discussionmentioning

confidence: 99%

Influence of sex on genetic regulation of “drinking in the dark” alcohol consumption

et al. 2015

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The ILSXISS (LXS) recombinant inbred (RI) panel of mice is a valuable resource for genetic mapping studies of complex traits, due to its genetic diversity and large number of strains. Male and female mice from this panel were used to investigate genetic influences on alcohol consumption in the “drinking in the dark” (DID) model. Male mice (38 strains) and female mice (36 strains) were given access to 20% ethanol during the early phase of their circadian dark cycle for four consecutive days. The first principal component of alcohol consumption measures on days 2, 3 and 4 was used as a phenotype (DID phenotype) to calculate QTLs, using a SNP marker set for the LXS RI panel. Five QTLs were identified, three of which included a significant genotype by sex interaction, i.e., a significant genotype effect in males and not females. To investigate candidate genes associated with the DID phenotype, data from brain microarray analysis (Affymetrix Mouse Exon 1.0 ST Arrays) of male LXS RI strains were combined with RNA-Seq data (mouse brain transcriptome reconstruction) from the parental ILS and ISS strains in order to identify expressed mouse brain transcripts. Candidate genes were determined based on common eQTL and DID phenotype QTL regions and correlation of transcript expression levels with the DID phenotype. The resulting candidate genes (in particular, Arntl/Bmal1) focused attention on the influence of circadian regulation on the variation in the DID phenotype in this population of mice.

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“…Per2 mutant/ knockout mice and Bmal1-knockout mice were reported to exhibit normal FAA or reduced FAA in different studies performed in different laboratories (118 -121). Recently, Mieda and Sakurai (122) showed that nervous system-specific Bmal1 deletion caused a reduction in the entrainment ability of the scheduled-feeding paradigm, suggesting that Bmal1 is an essential component of the FEO. Additionally, Takasu et al (123) demonstrated that clock-gene mutant or knockout mice have different abilities for adapting to different periodic feeding paradigms (T-cycle experiment).…”

Section: Food Anticipatory Activity (Faa)mentioning

confidence: 99%

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

Tahara¹,

Shibata²

2014

J Pharmacol Sci

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Molecular mechanisms of the circadian clock systemThe circadian clock system has been widely maintained in many species, from prokaryotes to mammals. "Circadian" means "around [a] day" in Latin, and therefore "circadian rhythm" refers to a cycle of approximate 24 h. The earth rotates once every 24 h, and the circadian system has evolved to adjust functions and behavior to this cycle in order to efficiently utilize sunlight for photosynthesis in the case of plants and cyanobacteria and to obtain food in the case of animals. One of the most important features of our circadian system is that circadian clocks can endogenously maintain time under constant darkness and without external stimuli, suggesting that our body has its own internal clocks. In 1972, Moore and Eichler (1) investigated the effects of destroying the suprachiasmatic nucleus (SCN) in the rat hypothalamus. Their results revealed the loss of sleep-wake cycles and corticosterone rhythms. Since then, the SCN is regarded as the location of the master clock system in mammals. The SCN receives light-dark information directly through the retinal-hypothalamic tract and organizes the local clock in the peripheral tissues through multiple pathways involving neural and hormonal functions (2, 3). The molecular mechanism of the circadian system in mammals has been well studied over the past two decades. The transcriptional-translational feedback loop of the major clock genes Bmal1, Clock, Per1/2, and Cry1/2 is the main component of the circadian system (2) (Fig. 1A). Bmal1 and Clock, which are transcriptional activators, play a positive role in activating the Per and Cry genes through a specific promoter sequence known as the E-box. Per and Cry are translated into proteins in the cytoplasm and are then transported back into the nucleus after interacting with each other, and they subsequently stop their transcription by binding to BMAL1 and CLOCK. Thus, Per and Cry are rhythmically expressed over a 24-h period. This transcriptional regulation induces rhythmic expression of approximately 10% of all genes in each peripheral cell (4 -6). In addition to such transcriptional regulation of the circadian clock, post-transcriptional regulation and translational regulation have recently been reported to play important roles in maintaining circadian rhythms. Genome-wide RNA-seq and Chip-seq analyses found that only 22% of the rhythmically oscillating messenger RNAs are driven by de novo transcription, with RNA polymerase II recruitment and chromatin remodeling also exhibiting such rhythms (7). Furthermore, it was reported that the non-transcriptional redox cycle has a 24-h rhythm in Chrono-biology, Chrono-pharmacology, and Chrono-nutrition Tokyo 162-8480, Japan Received October 25, 2013; Accepted January 5, 2014 Abstract. The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep-wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light-dark cycle, food...

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Bmal1in the Nervous System Is Essential for Normal Adaptation of Circadian Locomotor Activity and Food Intake to Periodic Feeding

Cited by 54 publications

References 24 publications

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Influence of sex on genetic regulation of “drinking in the dark” alcohol consumption

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

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