Dataset Information

Circadian disruption of hippocampus in an early senescence male mouse model.

ABSTRACT: Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice. Here we test the hypothesis that in this early senescence model, disruption of the molecular circadian clock in SAMP8 animals drives disrupted behavior and physiology. We found normal rhythms in PER2 protein expression in the SCN of SAMP8 animals at 4 months, despite the presence of disrupted wheel-running activity rhythms at this age. Interestingly, a significant rhythm in PER2 expression was not observed in the hippocampus of SAMP8 animals, despite a significant 24-h rhythm in SAMR1 controls. We also examined time-restricted feeding as a potential strategy to rescue disrupted hippocampal plasticity. Time-restricted feeding increased long-term potentiation at Schaffer collateral-CA1 synapses in SAMP8 mice (compared to SAMR1 controls). Overall, we confirm disrupted circadian locomotor rhythms in this early senescence model (as early as 4 months) and discovered that this disruption is not due to arrhythmic PER2 levels in the SCN; however, other extra-SCN circadian oscillators (i.e., hippocampus) are likely impaired with accelerated aging.

SUBMITTER: Davis JA

PROVIDER: S-EPMC9422145 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circadian disruption of hippocampus in an early senescence male mouse model.

Davis Jennifer A JA Paul Jodi R JR Mokashi Mugdha V MV Yates Stefani A SA Mount Daniel J DJ Munir Hira A HA Goode Lacy K LK Young Martin E ME Allison David B DB Gamble Karen L KL

Pharmacology, biochemistry, and behavior 20220418

Age-related cognitive decline and disruptions in circadian rhythms are growing problems as the average human life span increases. Multiple strains of the senescence-accelerated mouse (SAM) show reduced life span, and the SAMP8 strain in particular has been well documented to show cognitive deficits in behavior as well as a bimodal pattern of circadian locomotor activity. However, little is known about circadian regulation within the hippocampus of these strains of mice. Here we test the hypothes ...[more]

PMID: 35447158

Similar Datasets

Project description:Background: Disruption of natural light cycles, as experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer develop more severe disease when exposed to irregular light/dark cycles, supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis. In Eμ-MYC mice, which express transgenic c-MYC in B cells and develop aggressive lymphomas and leukemia, global Cry2 deletion reduces survival and enhances tumor formation. Lighting conditions that mimic the disruption experienced by shift workers dampen Cry2 transcripts in peripheral tissues of C57BL/6J mice. Although it is milder than homozygous deletion of Cry2, we hypothesized that reduced Cry2 rhythmicity could alter MYC protein accumulation and contribute to enhanced cancer risk caused by circadian disruption. We tested this hypothesis in MYC-driven lymphoma. Methods: We housed Eμ-MYC mice in light-tight boxes set to either control (continuous cycles of 12-hours of light followed by 12-hours of dark, LD12:12) or chronic jetlag (eight-hour light phase advances every two to three days, CJL) lighting conditions and assessed the impact of disrupted light cycles on survival and tumor formation in Eμ-MYC mice. Results: Environmental disruption of circadian rhythms did not alter tumor location, tumor growth, or survival in Eμ-MYC mice. Conclusions: Dampened rhythms of Cry2 following disruption of circadian light exposures is milder than deletion of Cry2. The lack of phenotype caused by altered circadian gene expression in contrast to enhanced tumorigenesis caused by homozygous deletion of Cry2 suggests that CRY2 dosage impacts this model. Importantly, these findings indicate that increased cancer risk associated with circadian disruption arises from one or more mechanisms that are not recapitulated here, and may be different in distinct tumor types.

Project description:BackgroundPlant senescence is the process of physiological maturation of plants and is important for crop yield and quality. Senescence is controlled by several factors, such as temperature and photoperiod. However, the molecular basis by which these genes promote senescence in soybeans is not well understood. We identified senescence-related genes via transcriptome analysis of early-senescence (ES)- and late-senescence (LS)-type plants to elucidate the molecular mechanisms of senescence in soybeans.ResultsWe obtained early-senescence (ES)- and late-senescence (LS)-type F7 plants from a cross between a hybrid (Glycine max × Glycine soja) and the Glycine max cultivar. The ES-type plants presented the reproductive (R2) growth stage at 50 days after sowing (DAS) and the R7 growth stage at 95 DAS, whereas the LS-type plants presented the beginning of the R1 and R6 growth stages at 50 and 95 DAS, respectively. To understand the molecular mechanisms underlying this senescence, we performed transcriptome analysis of leaves from 50 to 95 DAS of ES- and LS-type plants. A total of 2,414 and 2,471 genes at 50 and 95 DAS, respectively, were differentially expressed between ES-type and LS-type plants. Twenty-three candidate genes associated with the circadian clock, chlorophyll biosynthesis, phytohormones, and senescence-associated protein kinases were identified, and their expression levels were analyzed. In addition, to understand interaction between circadian clock and senescence, we analyzed expression patterns of seven circadian clock-related genes during the time period (light and dark condition): CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), CONSTANS-LIKE 9 (COL9), LUX ARRHYTHMO (LUX) EARLY FLOWERING 3 (ELF3), PSEUDO-RESPONSE REGULATOR5 (PRR5) and GIGANTEA (GI). The expression patterns of circadian clock-related genes were similar in the ES- and LS-type plants. However, the transcription levels of these genes were compared between ES- and LS-type plants, and the expression of these genes was greater than that in LS-type plants during the period when expression increased. Therefore, each set of candidate genes regulated senescence in each plant by regulating their expression level.ConclusionsThese findings provide novel insights into the regulation of senescence in soybean plants, which could lead to the development of new strategies to improve agriculture.

Dataset Information

Circadian disruption of hippocampus in an early senescence male mouse model.

Publications

Circadian disruption of hippocampus in an early senescence male mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets