Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons

Wang, Tongfei; Yu, Yanxun V.; Govindaiah, Gubbi; Ye, Xiaoying; Artinian, Liana; Coleman, Todd P.; Sweedler, Jonathan V.; Cox, Charles L.; Gillette, Martha U.

doi:10.1126/science.1222826

Cited by 195 publications

(208 citation statements)

References 32 publications

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“…Bmal1 KO mice exhibit increased ROS levels in spleen, kidney, and brain, and treatment with the glutathione precursor N-acetyl cysteine extends lifespan in these mice (9,22,53). The cellular redox state shows circadian oscillation, which is dependent on Bmal1 expression both in cultured fibroblasts and the mouse SCN (54,55). Furthermore, the acetylation of multiple critical mitochondrial proteins shows circadian oscillation, suggesting clock-mediated control of the mitochondrial redox state (56).…”

Section: Discussionmentioning

confidence: 99%

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Musiek¹,

Lim²,

Yang³

et al. 2013

J. Clin. Invest.

414

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: Discussionmentioning

confidence: 99%

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Musiek¹,

Lim²,

Yang³

et al. 2013

J. Clin. Invest.

414

448

View full text Add to dashboard Cite

show abstract

“…A general role for circadian regulation of redox state coupled to membrane excitability has been described recently in mammalian suprachiasmatic neurons (49). Redox modulation of circadian neural excitability may be a well-conserved feature.…”

Section: Discussionmentioning

confidence: 99%

CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor

Fogle

Baik

Houl

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

121

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Blue light activation of the photoreceptor CRYPTOCHROME (CRY) evokes rapid depolarization and increased action potential firing in a subset of circadian and arousal neurons in Drosophila melanogaster. Here we show that acute arousal behavioral responses to blue light significantly differ in mutants lacking CRY, as well as mutants with disrupted opsin-based phototransduction. Lightactivated CRY couples to membrane depolarization via a well conserved redox sensor of the voltage-gated potassium (K + ) channel β-subunit (Kvβ) Hyperkinetic (Hk). The neuronal light response is almost completely absent in hk −/− mutants, but is functionally rescued by genetically targeted neuronal expression of WT Hk, but not by Hk point mutations that disable Hk redox sensor function. Multiple K + channel α-subunits that coassemble with Hk, including Shaker, Ether-a-go-go, and Ether-a-go-go-related gene, are ion conducting channels for CRY/Hk-coupled light response. Light activation of CRY is transduced to membrane depolarization, increased firing rate, and acute behavioral responses by the Kvβ subunit redox sensor.phototransduction | potassium channel | redox | cryptochrome

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“…However, there are numerous circumstances in which metabolic processes causally control genetic ones (75)(76)(77), despite the fact that doing so requires a reversal of the normal explanatory order. The redox control of transcription in chloroplast-bearing cells is a clear illustration of how such a "reverse" explanation can work (77).…”

Section: Metabolic Evolutionary Explanationmentioning

confidence: 99%

Endosymbiosis and its implications for evolutionary theory

O’Malley

2015

Proc. Natl. Acad. Sci. U.S.A.

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Historically, conceptualizations of symbiosis and endosymbiosis have been pitted against Darwinian or neo-Darwinian evolutionary theory. In more recent times, Lynn Margulis has argued vigorously along these lines. However, there are only shallow grounds for finding Darwinian concepts or population genetic theory incompatible with endosymbiosis. But is population genetics sufficiently explanatory of endosymbiosis and its role in evolution? Population genetics "follows" genes, is replication-centric, and is concerned with vertically consistent genetic lineages. It may also have explanatory limitations with regard to macroevolution. Even so, asking whether population genetics explains endosymbiosis may have the question the wrong way around. We should instead be asking how explanatory of evolution endosymbiosis is, and exactly which features of evolution it might be explaining. This paper will discuss how metabolic innovations associated with endosymbioses can drive evolution and thus provide an explanatory account of important episodes in the history of life. Metabolic explanations are both proximate and ultimate, in the same way genetic explanations are. Endosymbioses, therefore, point evolutionary biology toward an important dimension of evolutionary explanation.endosymbiosis | evolutionary theory | macroevolution | eukaryogenesis | metabolism M any historical accounts have viewed organelle-producing endosymbioses and symbioses in general as competing conceptually against standard evolutionary theory. Although there are several older claims to this effect, I will focus on Lynn Margulis's conjectures about how endosymbioses can be interpreted as posing problems for neo-Darwinian evolutionary theory. My aim is to assess whether endosymbiosis does in fact put pressure on evolutionary biologists and philosophers of evolution to expand beyond gene frequencies and encompass alternative explanatory frameworks.Rather than agents of revolution bent on overthrowing evolutionary theory, it is more likely that endosymbiotic relationships offer their greatest explanatory value as model systems for macroevolution. Such systems can tell us a great deal about conflict and control dynamics in ongoing organismal interactions. They provide remarkable examples of enduring evolutionary game-changing mutualistic relationships, and call out for an account of why such relationships persist and become increasingly stable.However, instead of focusing on "informational" properties of organisms, endosymbiotic systems draw attention to metabolism as a central organizing feature of life. A metabolic perspective focuses explanatorily on biochemical networks rather than genes, on phenotypic interactions rather than informational inheritance, on communities in addition to isolated organisms and lineages, and on major diversifications in the history of life. "Endosymbiotic" views of evolution are therefore valuable for expanding evolutionary explanations, even if they do not constitute a fullblown theoretical alternative to standard evolutionary...

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Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons

Cited by 195 publications

References 32 publications

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor

Endosymbiosis and its implications for evolutionary theory

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