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Updated: Mar 7, 2026
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
miR-149 and miR-29c as candidates for bipolar disorder biomarkers
Jason L Choi1, Patricia F Kao1, Elena Itriago1
1Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
Abstract:
Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients. In this study, we show that EVs extracted from the anterior cingulate cortex (BA24), a crucial area for modulating emotional expression and affect, have increased levels of miR-149 in BD patients compared to controls. Because miR-149 has been shown to inhibit glial proliferation, increased miR-149 expression in BA24-derived EVs is consistent with the previously reported reduced glial cell numbers in BA24 of patients diagnosed with either familial BD or familial major depressive disorder. qPCR analysis of laser-microdissected neuronal and glial cells from BA24 cortical samples of BD patients verified that the glial, but not neuronal, population exhibits significantly increased miR-149 expression. Finally, we report altered expression of both miR-149 and miR-29c in EVs extracted from brains of Flinders Sensitive Line rats, a well-validated animal model exhibiting depressive-like behaviors and glial (astrocytic) dysfunction. These findings warrant future investigations into the potential of using EV miRNA signatures as biomarkers to further enhance the biological definition of BD. © 2017 Wiley Periodicals, Inc.
Insights
Altered microRNA (miRNA) levels in brain extracellular vesicles (EVs) may indicate bipolar disorder (BD) pathology. This study found increased miR-149 in anterior cingulate cortex EVs from BD patients, suggesting a potential biomarker for this condition.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Bipolar disorder (BD) pathogenesis remains unclear, but altered microRNA (miRNA) levels in the brain are implicated.
- Previous research identified altered miR-29c in extracellular vesicles (EVs) from the prefrontal cortex of BD patients.
Purpose of the Study:
- To investigate miRNA alterations in extracellular vesicles (EVs) from the anterior cingulate cortex (BA24) in bipolar disorder (BD).
- To explore the role of miR-149 in glial cells within the anterior cingulate cortex (BA24) of BD patients.
- To examine miRNA expression in a validated animal model of BD.
Main Methods:
- Extracellular vesicles (EVs) were extracted from the anterior cingulate cortex (BA24) of bipolar disorder (BD) patients and controls.
- Quantitative PCR (qPCR) was used to analyze miR-149 and miR-29c levels in EVs and laser-microdissected neuronal and glial cells.
- EVs and brain tissue from Flinders Sensitive Line rats, an animal model for BD, were analyzed for miRNA expression.
Main Results:
- EVs from the anterior cingulate cortex (BA24) of BD patients showed increased miR-149 levels compared to controls.
- Glial cells, but not neuronal cells, in the BA24 region of BD patients exhibited significantly increased miR-149 expression.
- Altered expression of miR-149 and miR-29c was observed in EVs from the brains of Flinders Sensitive Line rats.
Conclusions:
- Increased miR-149 in anterior cingulate cortex (BA24) EVs may contribute to the reduced glial cell numbers observed in bipolar disorder (BD).
- These findings suggest that EV miRNA signatures, specifically miR-149 and miR-29c, could serve as potential biomarkers for bipolar disorder (BD).
- Further research is warranted to validate EV miRNAs as diagnostic or prognostic tools for BD.
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