Rapid Jetlag Resetting of Behavioral, Physiological, and Molecular Rhythms in Proestrous Female Mice

Pilorz, Violetta; Kolms, Beke; Oster, Henrik

doi:10.1177/0748730420965291

Cited by 7 publications

(6 citation statements)

References 121 publications

(134 reference statements)

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“…Although activity rhythms were disrupted by 8 h advance and delay phase shifts, daily vaginal smears indicated that with very few exceptions estrous cycles were not interrupted in either genotype (data not shown). In contrast to observations in mice ( Pilorz, et al, 2020 ), the latency to re-entrain was unaffected in either genotype by the day of the estrous cycle on which hamsters were subjected to 8 h advances or delays.…”

Section: Resultscontrasting

confidence: 98%

Adult Neurogenesis Is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters

Bahiru

Bittman

2023

eNeuro

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Cell birth and survival in the adult hippocampus are regulated by a circadian clock. Rotating shift work and jet lag disrupt circadian rhythms and aggravate disease. Internal misalignment, a state in which abnormal phase relationships prevail between and within organs, is proposed to account for adverse effects of circadian disruption. This hypothesis has been difficult to test because phase shifts of the entraining cycle inevitably lead to transient desynchrony. Thus, it remains possible that phase shifts, regardless of internal desynchrony, account for adverse effects of circadian disruption and alter neurogenesis and cell fate.In order to address this question, we examined cell birth and differentiation in the duper Syrian hamster (Mesocricetus auratus), aCry1-null mutant in which re-entrainment of locomotor rhythms is greatly accelerated. Adult females were subjected to alternating 8h advances and delays at eight 16-day intervals. BrdU, a cell birth marker, was given midway through the experiment. Repeated phase shifts decreased the number of newborn non-neuronal cells in wt, but not duper hamsters. The duper mutation increased the number of BrdU-ir cells that stained for NeuN, which marks neuronal differentiation. Immunocytochemical staining for proliferating cell nuclear antigen (PCNA) indicated no overall effect of genotype or repeated shifts on cell division rates at the time of sacrifice. Cell differentiation, assessed by doublecortin (DCX), was higher in duper hamsters but was not significantly altered by repeated phase shifts. Our results support the internal misalignment hypothesis, and indicate thatCry1regulates cell differentiation. Phase shifts may determine neuronal stem cell survival and time course of differentiation after cell birth.Significance StatementThe birth of neurons in adult brain impacts learning and memory. Circadian disruption, such as occurs in jet lag, adversely affects neurogenesis. It is unclear whether shifts of the light:dark cycle are inherently deleterious, or whether misalignment of the phase of circadian oscillators is responsible. Repeated shifts decreased the number of non-neuronal cells born in adult dentate gyrus of wild type hamsters, but increased the percentage that developed neuronal phenotype. Duper mutants, which are deficient in the core clock geneCryptochrome 1and re-entrain 4 times as fast as wild types, experienced increased neurogenesis but showed no effect of phase shifts. These results implicateCry1in regulation of neurogenesis and indicate that circadian misalignment is critical in jet lag.

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Section: Resultscontrasting

confidence: 98%

Adult Neurogenesis Is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters

Bahiru

Bittman

2023

eNeuro

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“…They suggest that E2, acting via ERβ in the SCN rich in ERs, enhances circuitry coupling and reveals an additional function of E2 in astrocytes, influencing rhythmicity within SCN neurons. These observations propose that estrogen-mediated coupling could fortify the SCN, rendering it more resilient against environmental alterations, as observed in our recent study (Pilorz, Kolms, & Oster, 2020) during elevated E2 levels in the estrus cycle.…”

Section: Discussionsupporting

confidence: 79%

Estrogen‐mediated coupling via gap junctions in the suprachiasmatic nucleus

Schlaeger,

Olejniczak,

Lehmann

et al. 2024

Eur J of Neuroscience

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The circadian clock orchestrates many physiological and behavioural rhythms in mammals with 24‐h periodicity, through a hierarchical organisation, with the central clock located in the suprachiasmatic nucleus (SCN) in the hypothalamus. The circuits of the SCN generate circadian rhythms with precision, relying on intrinsic coupling mechanisms, for example, neurotransmitters like arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), neuronal gamma‐aminobutyric acid (GABA) signalling and astrocytes connected by gap junctions composed of connexins (Cx). In female rodents, the presence of estrogen receptors (ERs) in the dorsal SCN suggests an influence of estrogen (E2) on the circuit timekeeping that could regulate circadian rhythm and coupling. To investigate this, we used SCN explants together with hypothalamic neurons and astrocytes. First, we showed that E2 stabilised the circadian amplitude in the SCN when rAVPs (receptor‐associated vasopressin peptides) were inhibited. However, the phase delay induced by VIPAC2 (VIP receptors) inhibition remained unaffected by E2. We then showed that E2 exerted its effects in the SCN via ERβ (estrogen receptor beta), resulting in increased expression of Cx36 and Cx43. Notably, specific inhibition of both connexins resulted in a significant reduction in circadian amplitude within the SCN. Remarkably, E2 restored the period with inhibited Cx36 but not with Cx43 inhibition. This implies that the network between astrocytes and neurons, responsible for coupling in the SCN, can be reinforced through E2. In conclusion, these findings provide new insights into how E2 regulates circadian rhythms ex vivo in an ERβ‐dependent manner, underscoring its crucial role in fortifying the SCN's rhythm.

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“…Per2 m/m females undergo reproductive aging faster than males (Pilorz and Steinlechner, 2008), and we do not know how long-term DD affects estrous cycling.Given the impact of female reproductive hormones on circadian rhythms in general and Per2 in particular (Nakamura et al, 2005, 2008), processes associated with reproductive aging may contribute to the sex difference in arrhythmia identified here or in part mask the effect of loss of estrous cycling (Pilorz et al, 2020). Pilorz and Steinlechner (2008) identified reproductive senescence in female Per2 m/m mice as beginning sometime after 6 months of age, as 9- to 12-month-old Per2 m/m females had reduced fertility compared with WT controls.…”

Section: Discussionmentioning

confidence: 94%

Spontaneous Recovery of Circadian Organization in Mice Lacking a Core Component of the Molecular Clockwork

et al. 2021

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Circadian rhythms are generated by interlocked transcriptional-translational feedback loops of circadian clock genes and their protein products. Mice homozygous for a functional deletion in the Period-2 gene ( Per2m/m mice) exhibit short free-running circadian periods and eventually lose behavioral circadian rhythmicity in constant darkness (DD). We investigated Per2m/m mice in DD for several months and identified a categorical sex difference in the dependence on Per2 for maintenance of circadian rhythms. Nearly all female Per2m/m mice became circadian arrhythmic in DD, whereas free-running rhythms persisted in 37% of males. Remarkably, with extended testing, Per2m/m mice did not remain arrhythmic in DD, but after varying intervals spontaneously recovered robust, free-running circadian rhythms, with periods shorter than those expressed prior to arrhythmia. Spontaneous recovery was strikingly sex-biased, occurring in 95% of females and 33% of males. Castration in adulthood resulted in male Per2m/m mice exhibiting female-like levels of arrhythmia in DD, but did not affect spontaneous recovery. The circadian pacemaker of many gonad-intact males, but not females, can persist in DD for long intervals without a functional PER2 protein; their circadian clocks may be in an unstable equilibrium, incapable of sustaining persistent coherent circadian organization, resulting in transient cycles of circadian organization and arrhythmia.

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Rapid Jetlag Resetting of Behavioral, Physiological, and Molecular Rhythms in Proestrous Female Mice

Cited by 7 publications

References 121 publications

Adult Neurogenesis Is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters

Adult Neurogenesis Is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters

Estrogen‐mediated coupling via gap junctions in the suprachiasmatic nucleus

Spontaneous Recovery of Circadian Organization in Mice Lacking a Core Component of the Molecular Clockwork

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