Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock

Cao, Ruifeng; Lee, Bo-Young; Cho, Hee Yeon; Saklayen, Sanjida S.; Obrietan, Karl

doi:10.1016/j.mcn.2008.03.005

Cited by 78 publications

(85 citation statements)

References 82 publications

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“…Interestingly, N-methyl-D-aspartate (NMDA) antagonism alters glutamate-mediated light input to the central clock as well as PER expression (60, 61), which would be consistent with ketamine-altered light input to the central clock. However, the fact that ketamine has a half-life of 2.5 to three hours, and was infused mid-morning when the phase-shifting effects of light are negligible, argues against a direct effect of ketamine on light input per se .…”

Section: Discussionmentioning

confidence: 75%

Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine’s Rapid Antidepressant Properties

Duncan

Slonena

Hejazi

et al. 2017

Biological Psychiatry

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Background The rapid clinical antidepressant effects of the glutamatergic modulator ketamine may be due to its ability to restore synaptic plasticity and related effects on sleep-wake and circadian systems. Preclinical studies indicate that ketamine alters expression of circadian clock-associated molecules, and clinical studies of ketamine on plasticity-related biomarkers further suggest an association with sleep slow waves and sleep homeostasis. Methods Wrist activity monitors were used to examine the pharmacologic and rapid antidepressant effects of ketamine on markers of circadian timekeeping (amplitude and timing) in mood disorders. Circadian amplitude and timing of activity at baseline, post-infusion Day1 (D1), and Day3 (D3) were measured in 51 patients with major depressive disorder (MDD) or bipolar disorder (BD). Results Compared with either placebo or baseline, a mood-independent decrease of the central circadian value (mesor) was present on D1 after ketamine treatment. Mood-associated circadian effects between rapid (D1) responders and non-responders were found at baseline, D1, and D3. At baseline, a phase-advanced activity pattern and lower mesor distinguished subsequent responders from non-responders. On D1, ketamine non-responders had a lower mesor and a blunted 24-hour amplitude relative to baseline. On D3, patients with a persisting clinical response exhibited a higher amplitude and mesor compared with non-responders. Conclusions The findings are the first to demonstrate an association between ketamine’s clinical antidepressant effects and circadian timekeeping. The results suggest that trait-like circadian activity patterns indicate rapid mood response to ketamine, and that mediators of continuing ketamine-induced mood changes include altered timing and amplitude of the circadian system.

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Section: Discussionmentioning

confidence: 75%

Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine’s Rapid Antidepressant Properties

Duncan

Slonena

Hejazi

et al. 2017

Biological Psychiatry

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“…The blockage of miR-132 activity leads to reduced phase shifting after a light pulse, and miR-132 enhances Per1 protein expression after a light pulse (Cheng et al, 2007). In addition, the mammalian target of rapamycin (mTOR) pathway, a master regulator of translation, plays a significant role in the SCN clock (Cao, Anderson, Jung, Dziema, & Obrietan, 2011; Cao, Lee, Cho, Saklayen, & Obrietan, 2008; Cao, Li, Cho, Lee, & Obrietan, 2010) (Figure 1.5). The activity of mTOR is rhythmic in the SCN (Cao et al, 2011), and inhibition of mTOR activity leads to defective light-induced phase shifting of mouse activity rhythms (Cao et al, 2010).…”

Section: The Function Of Mapks In Circadian Input Pathwaysmentioning

confidence: 99%

Diverse Roles for MAPK Signaling in Circadian Clocks

Goldsmith

Bell-Pedersen

2013

Advances in Genetics

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The mitogen-activated protein kinase (MAPK) family of genes aids cells in sensing both extracellular and intracellular stimuli, and emerging data indicate that MAPKs have fundamental, yet diverse, roles in the circadian biological clock. In the mammalian sup-rachiasmatic nucleus (SCN), MAPK pathways can function as inputs allowing the endogenous clock to entrain to 24 h environmental cycles. MAPKs can also interact physically and/or genetically with components of the molecular circadian oscillator, implying that MAPKs can affect the cycling of the clock. Finally, circadian rhythms in MAPK pathway activation exist in many different tissue types and in model organisms, providing a mechanism to coordinately control the expression tissue-specific target genes at the proper time of day. As such, it should probably not come as a surprise that MAPK signaling pathways and circadian clocks affect similar biological processes and defects in either pathway lead to many of the same types of human diseases, highlighting the need to better define the mechanisms that link these two fundamental pathways together.

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“…Activity of the mTOR pathway in the suprachiasmatic nucleus (SCN) is stimulated by light and mutations in the mTOR kinase itself or in the mTOR effector protein eukaryotic initiation factor 4E binding protein (4E-BP) regulate circadian timing(Cao et al, 2011; Cao et al, 2015; Cao et al, 2008; Cao et al, 2010; Cao et al, 2013). Interestingly, mTOR pathway activity demonstrates circadian oscillations(Cao et al, 2013; Cornu et al, 2014; Jouffe et al, 2013; Khapre et al, 2014; Lipton et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy

Lipton¹,

Boyle²,

Yuan³

et al. 2017

Cell Reports

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SUMMARY Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder characterized by mutations in either the TSC1 or TSC2 genes whose products form a critical inhibitor of the mechanistic target of rapamycin (mTOR). Loss of TSC1/2 gene function renders an mTOR-overactivated state. Clinically, TSC manifests with epilepsy, intellectual disability, autism, and sleep dysfunction. Here we report that mouse models of TSC have abnormal circadian rhythms. We show that mTOR regulates the proteostasis of the core clock protein BMAL1, affecting its translation, degradation, and subcellular localization. This results in elevated levels of BMAL1 and a dysfunctional clock that displays abnormal timekeeping in constant conditions and exaggerated responses to phase resetting. Genetically lowering the dose of BMAL1 rescues circadian behavioral phenotypes in TSC mouse models. These findings indicate that BMAL1 deregulation is a feature of the mTOR-activated state and suggest a molecular mechanism for mitigating circadian phenotypes in a neurodevelopmental disorder.

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Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock

Cited by 78 publications

References 82 publications

Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine’s Rapid Antidepressant Properties

Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine’s Rapid Antidepressant Properties

Diverse Roles for MAPK Signaling in Circadian Clocks

Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy

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