bims-ciryme 2023-08-20 papers

Issue of 2023‒08‒20
three papers selected by
Gabriela Da Silva Xavier
University of Birmingham

F1000Res. 2023 ;12 762

The impact of shift-work light conditions on tissue-specific circadian rhythms of canonical clock genes: insights from a mouse model study.

Bala S C Koritala, Panshak P Dakup, Kenneth I Porter, Shobhan Gaddameedhi.

Background: The natural day-night cycle synchronizes our circadian rhythms, but modern work practices like night shifts disrupt this pattern, leading to increased exposure to nighttime light. This exposure is linked to various health issues. While some studies have explored the effects of night shifts on human circadian rhythms, there is limited research on the consequences of long-term exposure to shift-work light conditions. Rodents can provide valuable insights into these effects. This study aimed to examine how short- or long-term exposure to rotating shifts and chronic jetlag affects the core circadian oscillators in the liver and skin of mammals. Methods: C57BL/6J male mice were subjected to simulated shift-work light conditions, including short-term or long-term rotating shifts and chronic jet-lag conditions. Liver and skin samples were collected every four hours over a 24-hour period on the second day of constant darkness. RNA was extracted and qRT-PCR analysis was conducted to measure the circadian gene expression in liver and skin tissues. Circadian rhythm analysis using CircaCompare compared the control group to mice exposed to shift-work light conditions. Results: The liver's circadian clock is significantly altered in mice under long-term rotating shift conditions, with a lesser but still noticeable impact in mice experiencing chronic jetlag. However, short-term rotating shift conditions do not significantly affect the liver's circadian clock. Conversely, all three simulated shift conditions affect the skin's circadian clock, indicating that the skin clock is more sensitive to shift-work light conditions than the liver clock. Compared to the liver, the skin's circadian clock is greatly affected by long-term rotating shift conditions. Conclusions: The study findings indicate more pronounced disturbances in the canonical clock genes of the skin compared to the liver under simulated shift-work light conditions. These results suggest that the skin clock is more vulnerable to the effects of shift-work.

Keywords: Canonical clock genes; jet-lag; liver; mouse; rotating shift; skin.

DOI: https://doi.org/10.12688/f1000research.136998.2

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2023 Aug 17.

Maternal developmental history alters transfer of circadian clock genes to offspring in Japanese quail (Coturnix japonica).

Jessica Harvey-Carroll, Tyler J Stevenson, Karen A Spencer.

Maternal signals shape embryonic development, and in turn post-natal phenotypes. RNA deposition is one such method of maternal signalling and circadian rhythms are one trait thought to be maternally inherited, through this mechanism. These maternal circadian gene transcripts aid development of a functioning circadian system. There is increasing evidence that maternal signals can be modified, depending on prevailing environmental conditions to optimise offspring fitness. However, currently, it is unknown if maternal circadian gene transcripts, and consequently early embryonic gene transcription, are altered by maternal developmental conditions. Here, using avian mothers who experienced either pre-natal corticosterone exposure, and/or post-natal stress as juveniles we were able to determine the effects of the timing of stress on downstream circadian RNA deposition in offspring. We demonstrated that maternal developmental history does indeed affect transfer of offspring circadian genes, but the timing of stress was important. Avian mothers who experienced stress during the first 2 weeks of post-natal life increased maternally deposited transcript levels of two core circadian clock genes, BMAL1 and PER2. These differences in transcript levels were transient and disappeared at the point of embryonic genome transcription. Pre-natal maternal stress alone was found to elicit delayed changes in circadian gene expression. After activation of the embryonic genome, both BMAL1 and PER2 expression were significantly decreased. If both pre-natal and post-natal stress occurred, then initial maternal transcript levels of BMAL1 were significantly increased. Taken together, these results suggest that developmental stress differentially produces persistent transgenerational effects on offspring circadian genes.

Keywords: Avian; Circadian; Circadian ontogeny; Clock genes; Maternal transfer

DOI: https://doi.org/10.1007/s00359-023-01666-2

Nat Commun. 2023 Aug 18. 14(1): 5027

A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer's disease mouse model.

Andrew E Warfield, Pooja Gupta, Madison M Ruhmann, Quiana L Jeffs, Genevieve C Guidone, Hannah W Rhymes, McKenzi I Thompson, William D Todd.

Alzheimer's disease (AD) patients exhibit progressive disruption of entrained circadian rhythms and an aberrant circadian input pathway may underlie such dysfunction. Here we examine AD-related pathology and circadian dysfunction in the APPSwe-Tau (TAPP) model of AD. We show these mice exhibit phase delayed body temperature and locomotor activity with increases around the active-to-rest phase transition. Similar AD-related disruptions are associated with sundowning, characterized by late afternoon and early evening agitation and aggression, and we show TAPP mice exhibit increased aggression around this transition. We show such circadian dysfunction and aggression coincide with hyperphosphorylated Tau (pTau) development in lateral parabrachial (LPB) neurons, with these disturbances appearing earlier in females. Finally, we show LPB neurons, including those expressing dynorphin (LPBdyn), project to circadian structures and are affected by pTau, and LPBdyn ablations partially recapitulate the hyperthermia of TAPP mice. Altogether we link pTau in a brainstem circadian input pathway to AD-related disturbances relevant to sundowning.

DOI: https://doi.org/10.1038/s41467-023-40546-w