bims-ciryme 2020-09-06 papers

Sci Bull (Beijing). 2020 Aug 15. 65(15): 1268-1280

Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding.

Zhihui Zhang, Qiaocheng Zhai, Yue Gu, Tao Zhang, Zhengyun Huang, Zhiwei Liu, Yi Liu, Ying Xu.

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker that drives body temperature rhythm. Time-restricted feeding (TRF) has potential as a preventative or therapeutic approach against many diseases. The potential side effects of TRF remain unknown. Here we show that a 4-hour TRF stimulus in mice can severely impair body temperature homeostasis and can result in lethality. Nearly half of the mice died at 21 °C, and all mice died at 18 °C during 4-hour TRF. Moreover, this effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis, which is different from "torpor", an adaptive response under food deprivation. Disrupting the circadian clock by the SCN lesions or a non-invasive method (constant light) which disrupts circadian clock rescued lethality during TRF. Analysis of circadian gene expression in the dorsomedial hypothalamus (DMH) demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes, such as Ccr5 and Calcrl, which are involved in thermoregulation. We demonstrate a side effect of 4-hour TRF on the homeostasis of body temperature and a rescue function by impairing the SCN function. Altogether, our results suggested that constructing a circadian arrhythmicity may have a beneficial effect on the host response to an acute stress.

Keywords: Body temperature; Circadian Clock; Hypothermia; The dorsomedial hypothalamus; The suprachiasmatic nucleus; Time-restricted feeding

DOI: https://doi.org/10.1016/j.scib.2020.03.025

FASEB J. 2020 Aug 31.

Brief light exposure at dawn and dusk can encode day-length in the neuronal network of the mammalian circadian pacemaker.

Anneke H O Olde Engberink, Job Huisman, Stephan Michel, Johanna H Meijer.

The central circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), is important for daily as well as seasonal rhythms. The SCN encodes seasonal changes in day length by adjusting phase distribution among oscillating neurons thereby shaping the output signal used for adaptation of physiology and behavior. It is well-established that brief light exposure at the beginning and end of the day, also referred to as "skeleton" light pulses, are sufficient to evoke the seasonal behavioral phenotype. However, the effect of skeleton light exposure on SCN network reorganization remains unknown. Therefore, we exposed mice to brief morning and evening light pulses that mark the time of dawn and dusk in a short winter- or a long summer day. Single-cell PER2::LUC recordings, electrophysiological recordings of SCN activity, and measurements of GABA response polarity revealed that skeleton light-regimes affected the SCN network to the same degree as full photoperiod. These results indicate the powerful, yet potentially harmful effects of even relatively short light exposures during the evening or night for nocturnal animals.

Keywords: GABA; light pollution; plasticity; seasonal; suprachiasmatic nucleus

DOI: https://doi.org/10.1096/fj.202001133RR

Cell. 2020 Aug 21. pii: S0092-8674(20)30994-6. [Epub ahead of print]

The Human and Mouse Enteric Nervous System at Single-Cell Resolution.

Eugene Drokhlyansky, Christopher S Smillie, Nicholas Van Wittenberghe, Maria Ericsson, Gabriel K Griffin, Gokcen Eraslan, Danielle Dionne, Michael S Cuoco, Max N Goder-Reiser, Tatyana Sharova, Olena Kuksenko, Andrew J Aguirre, Genevieve M Boland, Daniel Graham, Orit Rozenblatt-Rosen, Ramnik J Xavier, Aviv Regev.

The enteric nervous system (ENS) coordinates diverse functions in the intestine but has eluded comprehensive molecular characterization because of the rarity and diversity of cells. Here we develop two methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling. The 1,187,535 nuclei in our mouse atlas include 5,068 neurons from the ileum and colon, revealing extraordinary neuron diversity. We highlight circadian expression changes in enteric neurons, show that disease-related genes are dysregulated with aging, and identify differences between the ileum and proximal/distal colon. In humans, we profile 436,202 nuclei, recovering 1,445 neurons, and identify conserved and species-specific transcriptional programs and putative neuro-epithelial, neuro-stromal, and neuro-immune interactions. The human ENS expresses risk genes for neuropathic, inflammatory, and extra-intestinal diseases, suggesting neuronal contributions to disease.

Keywords: ENS; GWAS; aging; circadian; colon; enteric nervous system; enteric neuron; ileum; neuro-immune; single cell

DOI: https://doi.org/10.1016/j.cell.2020.08.003