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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Bipolar Disorder01:30

Bipolar Disorder

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Bipolar disorder is a chronic mental health condition marked by significant mood fluctuations, including episodes of mania and depression. Elevated energy levels, heightened mood or irritability, impulsive behavior, reduced sleep needs, rapid speech, racing thoughts, inflated self-esteem, and distractibility characterize mania. Individuals with bipolar disorder often alternate between depressive and manic states, with periods of emotional stability lasting an average of six months to a year.
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  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Differential Contributions Of Circadian Clock Genes To Cell Survival In Bipolar Disorder Patient Derived Neuronal Progenitor Cells Distinguishes Lithium Responders And Non-responders.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Differential Contributions Of Circadian Clock Genes To Cell Survival In Bipolar Disorder Patient Derived Neuronal Progenitor Cells Distinguishes Lithium Responders And Non-responders.

Related Experiment Video

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

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Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders.

Himanshu K Mishra1, Heather Wei2, Melissa LeRoux1

  • 1UC San Diego.

Research Square
|May 15, 2024

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
apoptosisbipolar disordercircadian rhythmlithium

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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

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Related Experiment Videos

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures

Published on: November 11, 2016

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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Circadian clock gene disruptions in bipolar disorder (BD) neurons impact cell survival and lithium response. Understanding these mechanisms may improve lithium treatment for BD patients.

Area of Science:

  • Neuroscience
  • Chronobiology
  • Genetics

Background:

  • Bipolar disorder (BD) involves disrupted circadian rhythms and neuronal loss, with variable lithium treatment response.
  • Lithium is a key neuroprotective treatment for BD, but its efficacy varies among patients.
  • Previous studies linked circadian rhythms in BD neurons to lithium response (Li-R) or non-response (Li-NR), but cellular mechanisms are unclear.

Approach:

  • Investigated interactions between circadian clock genes (PER1, BMAL1, REV-ERBα) and cell survival in mouse neurons and patient-derived neuronal progenitor cells (NPCs).
  • Utilized apoptosis assays with staurosporine (STS) and tested small molecule modulators of ROR/REV-ERB nuclear receptors.
  • Examined gene expression profiles following STS and GSK4112 treatments to identify BD- and Li-R-associated differences.
neuronal progenitor cell
stem cell

Key Points:

  • Lithium demonstrated neuroprotective effects in apoptosis assays.
  • Knockdown of PER1, BMAL1, and REV-ERBα differentially affected cell survival in various models.
  • Reduced PER1/BMAL1 expression increased cell death in Li-NR vs. Li-R NPCs; reduced REV-ERBα increased cell death in BD vs. control NPCs.
  • The REV-ERB agonist GSK4112 was neuroprotective in control cells but not in BD NPCs.

Conclusions:

  • Neuroprotective response to lithium is comparable in NPCs from Li-R and Li-NR individuals.
  • Circadian clock gene knockdown and REV-ERB modulation reveal distinct cellular vulnerabilities in BD patient NPCs.
  • These findings highlight specific mechanisms contributing to cell death in BD and may help predict lithium response.