Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis

Zhang, Xuebing; Huang, Suihong; Kim, Jin Young

doi:10.1016/j.isci.2024.108829

iScience

2024

DOI: 10.1016/j.isci.2024.108829

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Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis

Xuebing Zhang,

Suihong Huang,

Jin Young Kim

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2024

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Cited by 2 publications

References 47 publications

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BMAL1—Potential Player of Aberrant Stress Response in Q31L Mice Model of Affective Disorders: Pilot Results

Smirnova,

Amstislavskaya,

Smirnova

2024

IJMS

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Dysregulation in the stress-response system as a result of genetical mutation can provoke the manifestation of affective disorders under stress conditions. Mutations in the human DISC1 gene is one of the main risk factors of affective disorders. It was known that DISC1 regulates a large number of proteins including BMAL1, which is involved in the regulation of glucocorticoid synthesis in the adrenal glands and the sensitivity of glucocorticoid receptor target genes. Male mice with a point mutation Q31L in the Disc1 gene were exposed to chronic unpredictable stress (CUS), after which the behavioral and physiological stress response assessed. To assess whether there were any changes in BMAL1 in key brain regions involved in the stress response, immunohistochemistry was applied. It was shown that the Q31L mice had an aberrant behavioral response, especially to the 2 weeks of CUS, which was expressed in unchanged motor activity, increased time of social interaction, and alterations in anxiety and fear-related behavior. Q31L males did not show an increase in blood corticosterone levels after CUS and a decrease in body weight. Immunohistochemical analysis in intact Q31L mice revealed a decrease in BMAL1 immunofluorescence in the CA1 hippocampal area and lateral habenula. Thus, the Q31L mutation of the Disc1 gene disrupts behavioral and physiological stress response and the BMAL1 dysregulation may underlie it, so this protein can act as a molecular target for the treatment of affective disorders.

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BMAL1—Potential Player of Aberrant Stress Response in Q31L Mice Model of Affective Disorders: Pilot Results

Smirnova,

Amstislavskaya,

Smirnova

2024

IJMS

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Circadian Influences on Brain Lipid Metabolism and Neurodegenerative Diseases

Hussain,

Dar,

Pan

2024

Metabolites

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Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep–wake cycles, hormone secretion, and metabolism. These rhythms are controlled by the brain’s suprachiasmatic nucleus, which synchronizes with environmental signals, such as light and temperature, and consequently maintains alignment with the day–night cycle. Molecular feedback loops, driven by core circadian “clock genes”, such as Clock, Bmal1, Per, and Cry, are essential for rhythmic gene expression; disruptions in these feedback loops are associated with various health issues. Dysregulated lipid metabolism in the brain has been implicated in the pathogenesis of neurological disorders by contributing to oxidative stress, neuroinflammation, and synaptic dysfunction, as observed in conditions such as Alzheimer’s and Parkinson’s diseases. Disruptions in circadian gene expression have been shown to perturb lipid regulatory mechanisms in the brain, thereby triggering neuroinflammatory responses and oxidative damage. This review synthesizes current insights into the interconnections between circadian rhythms and lipid metabolism, with a focus on their roles in neurological health and disease. It further examines how the desynchronization of circadian genes affects lipid metabolism and explores the potential mechanisms through which disrupted circadian signaling might contribute to the pathophysiology of neurodegenerative disorders.

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Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis

Cited by 2 publications

References 47 publications

BMAL1—Potential Player of Aberrant Stress Response in Q31L Mice Model of Affective Disorders: Pilot Results

BMAL1—Potential Player of Aberrant Stress Response in Q31L Mice Model of Affective Disorders: Pilot Results

Circadian Influences on Brain Lipid Metabolism and Neurodegenerative Diseases

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