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Transcriptome Alterations in ASMT Knockout-Induced Depression-Like Behaviors and Exercise Effects

ABSTRACT: Sleep disorder caused by abnormal circadian rhythm is one of the main symptoms and risk factors of depression. N-acetylserotonin methyltransferase (ASMT), the last rate-limiting enzyme of melatonin (MT, a known hormone regulating circadian rhythms), has been reportedly associated with depression. Exercise can regulate circadian rhythm and play an important role in depression treatment. Recently, gene chip has been widely used in depression research. In the present study, we showed that ASMT knockout induced depression-like behaviors, which were ameliorated by swimming exercise. Moreover, swimming exercise increased serum levels of MT and 5-HT in ASMT knockout mice. In addition, transcriptome analysis identified 10 differentially expressed genes (DEGs) in KO mice compared with WT mice, and 29 DEGs in KO mice after swimming exercise. Among the DEGs, the direction and magnitude of change in Eps8l1 and Plcb2 were confirmed by qRT-PCR partly. Subsequent bioinformatic analysis showed that p53 signaling pathway, long-term depression and estrogen signaling pathway were enriched significantly. In the protein-protein interaction (PPI) networks, Mpp1 and Pidd1 were hub genes. These findings may provide new targets for the treatment of circadian rhythm-associated depression.

ORGANISM(S): Mus musculus

PROVIDER: GSE197888 | GEO | 2022/03/06

REPOSITORIES: GEO

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Project description:Objective The objective of the current trial is to investigate the effect of perioperative sleep and circadian rhythm on the natural course of survival among patient diagnosed with colorectal cancer. Concurrently, outcome measures like depression, fatigue, quality of life, and co-morbidity will be measured continuously in the short-, intermediate- and long-term period following diagnosis. The a-priori hypothesis is that preoperative sleep and circadian disturbances is a prognostic marker of reduced overall survival. Likewise, preoperative sleep-wake disturbances at baseline are expected to result in overall universally reduced quality of life, increased depression and fatigue. Furthermore, development of sleep-wake disturbances in the postoperative period as compared to preoperative sleep-wake rhythm is expected to a prognostic marker of negative outcomes. Target and study population The study population are all patients diagnosed with colorectal cancer in Region Zealand recruited consecutively from the trial initiation until study end each patient with an intended 5 year follow-up period. All available cases will be included in the trial. Study design The study will be an observational prospective cohort study applying a longituditional repeated measure design. Exposures and outcomes of interest The primary outcomes in the trial are sleep and circadian outcomes measured via actigraphy in the perioperative period. Furthermore, cancer related survival and overall survival in the 5 year follow-up period is considered primary outcomes. Secondary outcomes consist of consecutively measured depression, fatigue, quality of life, follow-up treatment and co-morbidity. Exposure variables are primary related to the cancer, i.e. cancer stage, surgical treatment, oncological treatment, baseline co-morbidity and pharmacological treatment. Some of the secondary outcomes could be expected to serve as confounding or mediating factors. Meaningful control for confounding will in the analysis phase be cancer stage and baseline sleep-wake rhythm status. Sampling methods All available cases will be sought included in the trial. No formal sample size has been performed and continues inclusion into the trial will be performed during an 1,5 year period. Statistical analyses The relationship between overall survival and baseline sleep-wake rhythm will be investigated using survival statistics and/or multivariate logistic regression. Expected results The investigators expect to see a marked difference in overall survival among patients with sleep and circadian disturbances at baseline.

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Transcriptome Alterations in ASMT Knockout-Induced Depression-Like Behaviors and Exercise Effects

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