bims-ciryme 2019-10-06 papers

Curr Top Behav Neurosci. 2019 Oct 05.

Circadian Regulation of the Brain and Behavior: A Neuroendocrine Perspective.

Neuroendocrine systems are key regulators of brain and body functions, providing an important nexus between internal states and the external world, which then modulates appropriate behavioral outputs. Circadian (daily) rhythms are endogenously generated rhythms of approximately 24 h that help to synchronize internal physiological processes and behavioral states to the external environmental light-dark cycle. Given the importance of timing (hours, days, annual) in many different neuroendocrine axes, understanding how the circadian timing system regulates neuroendocrine function is particularly critical. Similarly, neuroendocrine signals can significantly affect circadian timing, and understanding these mechanisms can provide insights into general concepts of neuroendocrine regulation of brain circuits and behavior. This chapter will review the circadian timing system and its control of two key neuroendocrine systems: the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) axis. It will also discuss how outputs from these axes feedback to affect the circadian clock. Given that disruption of circadian timing is a central component of many mental and physical health conditions and that neuroendocrine function is similarly implicated in many of the same conditions, understanding these links will help illuminate potentially shared causality and perhaps lead to a better understanding of how to manipulate these systems when they begin to malfunction.

Keywords: Androgen; Corticosterone; Cortisol; Estrogen; Reproduction; Stress; Suprachiasmatic

DOI: https://doi.org/10.1007/7854_2019_115

Cell Mol Life Sci. 2019 Sep 27.

Circadian regulation of astrocyte function: implications for Alzheimer's disease.

Celia A McKee, Brian V Lananna, Erik S Musiek.

The circadian clock regulates rhythms in gene transcription that have a profound impact on cellular function, behavior, and disease. Circadian dysfunction is a symptom of aging and neurodegenerative diseases, and recent studies suggest a bidirectional relationship between impaired clock function and neurodegeneration. Glial cells possess functional circadian clocks which may serve to control glial responses to daily oscillations in brain activity, cellular stress, and metabolism. Astrocytes directly support brain function through synaptic interactions, neuronal metabolic support, neuroinflammatory regulation, and control of neurovascular coupling at blood and CSF barriers. Emerging evidence suggests that the astrocyte circadian clock may be involved in many of these processes, and that clock disruption could influence neurodegeneration by disrupting several aspects of astrocyte function. Here we review the literature surrounding circadian control of astrocyte function in health and disease, and discuss the potential implications of astrocyte clocks for neurodegeneration.

Keywords: Alzheimer’s disease; Astrocyte; Circadian rhythms; Neurodegeneration

DOI: https://doi.org/10.1007/s00018-019-03314-y

Sci Immunol. 2019 Oct 04. pii: eaax1215. [Epub ahead of print]4(40):

A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut.

Fei Teng, Jeremy Goc, Lei Zhou, Coco Chu, Manish A Shah, Gérard Eberl, Gregory F Sonnenberg.

Group 3 innate lymphoid cells (ILC3s) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3s remain incompletely defined. Here, we identify that intestinal ILC3s are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations, and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in markedly reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3s exhibit impaired expression of Nr1d1 and Per3, hyperactivation of RORγt-dependent target genes, and elevated proapoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyperactivation of BMAL1-deficient ILC3s and restored cellular homeostasis in the intestine. Last, ILC3s isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3s in the presence of a complex intestinal microbiota and that this pathway is disrupted in the context of IBD.

DOI: https://doi.org/10.1126/sciimmunol.aax1215