Conditional Knockout of Bmal1 in Corticotropin-Releasing Factor Neurons Does Not Alter Sleep–Wake Rhythm in Mice

Hung, Chi Jung; Yamanaka, Akihiro; Ono, Daisuke

doi:10.3389/fnins.2021.808754

Cited by 2 publications

(3 citation statements)

References 41 publications

(51 reference statements)

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“…Furthermore, Bmal1 knockout in adrenocorticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus, which has monosynaptic efferent from SCN neurons, induced alterations in the rhythms of neuronal calcium activity as well as corticosterone release. However, in mice with Bmal1 knockout in CRH neurons across all brain regions, circadian rhythm and sleep electroencephalograms remains intact [ 137 ].…”

Section: Pathological Phenotypes Arising From Bmal1 ...mentioning

confidence: 99%

Neural function of Bmal1: an overview

et al. 2023

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Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research.

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Section: Pathological Phenotypes Arising From Bmal1 ...mentioning

confidence: 99%

Neural function of Bmal1: an overview

et al. 2023

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“…[13] BMAL1 deletion in homozygous mice attenuated the sleep rhythm, duration, and quality. [14] BMAL1 knockout cynomolgus monkeys exhibited improved nocturnal locomotion and decreased sleep. [15] Banxia Shumi decoction (BSXM), first recorded in The Yellow Emperor's Inner Classic, comprises only 2 medicines: Pinelliae rhizoma (Banxia) and Sorghum vulgare (Shumi); it is already widely used in the clinical treatment of insomnia disorders.…”

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment

Zhang

Zhang²,

Wang³

et al. 2023

Medicine

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Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.Abbreviations: BCL2L1 = BCL2 like 1, BSXM = Banxia Shumi decoction, DEGs = differentially expressed genes, EGFR = epidermal growth factor receptor, FOXO = forkhead box O, GO = gene ontology, GA = gondoic acid, GSEA = gene set enrichment analysis, KEGG = Kyoto Encyclopedia of Genes and Genomes, MAPK14 = mitogen-activated protein kinase, MCC = maximum cluster centrality, PPI = protein-protein interaction, ROC = receiver operating characteristic, SD = sleep deprivation, TCM = traditional Chinese medicine.

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Conditional Knockout of Bmal1 in Corticotropin-Releasing Factor Neurons Does Not Alter Sleep–Wake Rhythm in Mice

Cited by 2 publications

References 41 publications

Neural function of Bmal1: an overview

Neural function of Bmal1: an overview

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment

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