Vasopressin regulates daily rhythms and circadian clock circuits in a manner influenced by sex

Rohr, Kayla E.; Telega, Adam; Savaglio, Alexandra; Evans, Jennifer

doi:10.1016/j.yhbeh.2020.104888

Cited by 19 publications

(16 citation statements)

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“…A sex difference in the role of AVP in circadian timekeeping is consistent with previous work using an AVP-deficient mouse [30, 37]. In this genetic model, AVP deficiency decreased the precision of free-running locomotor rhythms and increased the duration of the active phase in both sexes, but only female AVP-deficient mice displayed longer period under free-running conditions [30]. Combined with the present results, these data indicate that AVP regulates multiple properties of circadian timekeeping and that these effects can differ by sex.…”

Section: Discussionsupporting

confidence: 90%

“…Similar to the lack of large male SCN responses to V1A/B agonists, male hamsters do not display behavioral resetting when AVP is injected into the SCN region in vivo [42]. A sex difference in the role of AVP in circadian timekeeping is consistent with previous work using an AVP-deficient mouse [30,37]. In this genetic model, AVP deficiency decreased the precision of free-running locomotor rhythms and increased the duration of the active phase in both sexes, but only female AVP-deficient mice displayed longer period under free-running conditions [30].…”

Section: Scn Resetting Induced By V1a/b Agonists Is Influenced By Bio...supporting

confidence: 87%

“…Further, G αq signaling is implicated in SCN resetting [25][26][27], which is important for entrainment of the circadian system. Last, daily rhythms in locomotor behavior are altered by the loss of AVP, V1A, and/or V1B [28][29][30], with some effects localized to the SCN itself [29] and with sex differences in the resulting phenotype [30]. Despite this work, it remains unclear whether V1 signaling directly influences the SCN molecular clock, how it might do so, and whether this response differs by sex.…”

Section: Introductionmentioning

confidence: 99%

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Vasopressin Resets the Central Circadian Clock in a Manner Influenced by Sex and Vasoactive Intestinal Polypeptide Signaling

Rohr

Inda

Evans³

2021

Neuroendocrinology

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Circadian rhythms in behavior and physiology are programmed by the suprachiasmatic nucleus (SCN) of the hypothalamus. A subset of SCN neurons produce the neuropeptide arginine vasopressin (AVP), but it remains unclear whether AVP signaling influences the SCN clock directly. Here we test that AVP signaling acting through V1A and V1B receptors influences molecular rhythms in SCN neurons. V1 receptor agonists were applied ex vivo to PERIOD2::LUCIFERASE SCN slices, allowing for real-time monitoring of changes in molecular clock function. V1A/B agonists reset the phase of the SCN molecular clock in a time-dependent manner, with larger magnitude responses by the female SCN. Further, we find evidence that both Gq and Gs signaling pathways interact with V1A/B-induced SCN resetting, and that this response requires vasoactive intestinal polypeptide (VIP) signaling. Collectively, this work indicates that AVP signaling resets SCN molecular rhythms in conjunction with VIP signaling and in a manner influenced by sex. This highlights the utility of studying clock function in both sexes and suggests that signal integration in central clock circuits regulates emergent properties important for the control of daily rhythms in behavior and physiology.

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Section: Discussionsupporting

confidence: 90%

Section: Scn Resetting Induced By V1a/b Agonists Is Influenced By Bio...supporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Vasopressin Resets the Central Circadian Clock in a Manner Influenced by Sex and Vasoactive Intestinal Polypeptide Signaling

Rohr

Inda

Evans³

2021

Neuroendocrinology

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“…However, with the Vip cre created by Todd, et al, Bmal1 fl/fl :Vip cre/+ did not produce a locomotor or body temperature phenotype, whereas the one we report here is significantly different from the Bmal1 fl/fl alone. Vip cre/cre and Avp cre/cre expression alone and in the absence of flux alleles can impair peptide production, disrupt circadian rhythms, and confound interpretation (58)(59)(60). Because AVP and VIP signaling are both implicated in the LH surge, we used mice heterozygous for cre to focus on the effect of BMAL1 disruption.…”

Section: Discussionmentioning

confidence: 99%

Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S

Tonsfeldt

Cui²,

Lee³

et al. 2022

Front. Endocrinol.

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Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, Bmal1, are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsiveness to exogenous kisspeptin. Here, we explore the role of Bmal1 in suprachiasmatic nucleus (SCN) neuron populations known to project to the neuroendocrine axis. We generated four mouse lines using Cre/Lox technology to create conditional deletion of Bmal1 in arginine vasopressin (Bmal1fl/fl:Avpcre), vasoactive intestinal peptide (Bmal1fl/fl:Vipcre), both (Bmal1fl/fl:Avpcre+Vipcre), and neuromedin-s (Bmal1fl/fl:Nmscre) neurons. We demonstrate that the loss of Bmal1 in these populations has substantial effects on home-cage circadian activity and temperature rhythms. Despite this, we found that female mice from these lines demonstrated normal estrus cycles, fecundity, kisspeptin responsiveness, and inducible LH surge. We found no evidence of reproductive disruption in constant darkness. Overall, our results indicate that while conditional Bmal1 knockout in AVP, VIP, or NMS neurons is sufficient to disrupted locomotor activity, this disruption is insufficient to recapitulate the neuroendocrine reproductive effects of the whole-body Bmal1 knockout.

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“…Our study revealed that the circadian rhythm is affected by sex differences. The effects of hormones related to circadian rhythm occur in a sex-dependent manner [ 76 ]. In addition, sex hormones have been reported to regulate circadian rhythms and behavior [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging

Noh

Jung

Kim

et al. 2022

IJMS

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Background: Circadian rhythm is associated with the aging process and sex differences; however, how age and sex can change circadian regulation systems remains unclear. Thus, we aimed to evaluate age- and sex-related changes in gene expression and identify sex-specific target molecules that can regulate aging. Methods: Rat livers were categorized into four groups, namely, young male, old male, young female, and old female, and the expression of several genes involved in the regulation of the circadian rhythm was confirmed by in silico and in vitro studies. Results: Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the expression of genes related to circadian rhythms changed more in males than in females during liver aging. In addition, differentially expressed gene analysis and quantitative real-time polymerase chain reaction/western blotting analysis revealed that Nr1d1 and Nr1d2 expression was upregulated in males during liver aging. Furthermore, the expression of other circadian genes, such as Arntl, Clock, Cry1/2, Per1/2, and Rora/c, decreased in males during liver aging; however, these genes showed various gene expression patterns in females during liver aging. Conclusions: Age-related elevation of Nr1d1/2 downregulates the expression of other circadian genes in males, but not females, during liver aging. Consequently, age-related upregulation of Nr1d1/2 may play a more crucial role in the change in circadian rhythms in males than in females during liver aging.

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Vasopressin regulates daily rhythms and circadian clock circuits in a manner influenced by sex

Cited by 19 publications

References 50 publications

Vasopressin Resets the Central Circadian Clock in a Manner Influenced by Sex and Vasoactive Intestinal Polypeptide Signaling

Vasopressin Resets the Central Circadian Clock in a Manner Influenced by Sex and Vasoactive Intestinal Polypeptide Signaling

Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S

Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging

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