bims-ciryme 2020-10-25 papers

Diabetes. 2020 Oct 21. pii: db200192. [Epub ahead of print]

Induction of Core Circadian Clock Transcription Factor Bmal1 Enhances β Cell Function and Protects Against Obesity-Induced Glucose Intolerance.

Kuntol Rakshit, Aleksey V Matveyenko.

Type 2 diabetes mellitus (T2DM) is characterized by β cell dysfunction due to impaired glucose-stimulated insulin secretion (GSIS). Studies show that β cell circadian clocks are important regulators of GSIS and glucose homeostasis. These observations raise the question whether enhancement of the circadian clock in β cells will confer protection against β cell dysfunction under diabetogenic conditions. To test this we employed an approach by first generating mice with β cell-specific inducible overexpression of Bmal1 (core circadian transcription factor; β-Bmal1 OV ). We subsequently examined the effects of β-Bmal1 OV on the circadian clock, GSIS, islet transcriptome, and glucose metabolism in context of diet-induced obesity. We additionally tested the effects of circadian clock-enhancing small molecule Nobiletin on GSIS in mouse and human control and T2DM islets. We report that β-Bmal1 OV mice display enhanced islet circadian clock amplitude, augmented in vivo and in vitro GSIS and are protected against obesity-induced glucose intolerance. These effects were associated with increased expression of purported BMAL1-target genes mediating insulin secretion, processing, and lipid metabolism. Furthermore, exposure of isolated islets to Nobiletin enhanced β cell secretory function in Bmal1-dependent manner. This work suggests therapeutic targeting of the circadian system as a potential strategy to counteract β cell failure under diabetogenic conditions.

DOI: https://doi.org/10.2337/db20-0192

J Neurosci Res. 2020 Oct 20.

Time-restricted feeding prevents depressive-like and anxiety-like behaviors in male rats exposed to an experimental model of shift-work.

Natalí N Guerrero-Vargas, Carmen Zárate-Mozo, Mara A Guzmán-Ruiz, Alfredo Cárdenas-Rivera, Carolina Escobar.

Individuals who regularly shift their sleep timing, like night and/or shift-workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift-work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, and depression. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental health effects associated with circadian disruption. Here, we explored whether adult male Wistar rats exposed to an experimental model of shift-work (W-AL) developed depressive and/or anxiety-like behaviors and whether this was associated with neuroinflammation in brain areas involved with mood regulation. We also tested whether time-restricted feeding (TRF) to the active phase could ameliorate circadian disruption and therefore would prevent depressive and anxiety-like behaviors as well as neuroinflammation. In male Wistar rats, W-AL induced depressive-like behavior characterized by hypoactivity and anhedonia and induced increased anxiety-like behavior in the open field test. This was associated with increased number of glial fibrillary acidic protein and IBA-1-positive cells in the prefrontal cortex and basolateral amygdala. Moreover W-AL caused morphological changes in the microglia in the CA3 area of the hippocampus indicating microglial activation. Importantly, TRF prevented behavioral changes and decreased neuroinflammation markers in the brain. Present results add up evidence about the importance that TRF in synchrony with the light-dark cycle can prevent neuroinflammation leading to healthy mood states in spite of circadian disruptive conditions.

Keywords: RRID:AB_10972670; RRID:AB_2109645; RRID:AB_2313606; RRID:AB_2336126; RRID:RGD_13508588; RRID:SCR_002285; RRID:SCR_003070; anxiety-like behavior; circadian; depression-like behavior; entrainment; neuroinflammation; time-restricted feeding

DOI: https://doi.org/10.1002/jnr.24741

ILAR J. 2020 Oct 19. 60(2): 150-158

Relevance of Electrical Light on Circadian, Neuroendocrine, and Neurobehavioral Regulation in Laboratory Animal Facilities.

John P Hanifin, Robert T Dauchy, David E Blask, Steven M Hill, George C Brainard.

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses that oscillate with the 24 hour rhythm of the day include sleep and wakefulness, body temperature, hormonal secretion, and a wide range of other physiological parameters. Melatonin has been the chief neuroendocrine hormone studied, but acute light-induced effects on corticosterone as well as other hormones have also been observed. Within the last two decades, a new photosensory system in the mammalian eye has been discovered. A small set of retinal ganglion cells, previously thought to function as a visual output neuron, have been shown to be directly photosensitive and act differently from the classic photoreceptors of the visual system. Understanding the effects of light on mammalian physiology and behavior must take into account how the classical visual photoreceptors and the newly discovered ipRGC photoreceptor systems interact. Scientists and facility managers need to appreciate lighting impacts on circadian, neuroendocrine, and neurobehavioral regulation in order to improve lighting of laboratory facilities to foster optimum health and well-being of animals.

Keywords: Animal Facilities; Circadian; Lighting; Melatonin; Neurobehavioral; Neuroendocrine

DOI: https://doi.org/10.1093/ilar/ilaa010