Abnormalities in the migration of neural precursor cells in familial bipolar disorder.
Salil K SukumaranPradip PaulVishwesha GuttalBharath HollaAlekhya VemulaHarsimar BhattPiyush BishtKezia MathewRavi Kumar NadellaAnu Mary VargheseVijayalakshmi KalyanMeera PurushottamSanjeev JainAdbs ConsortiumReeteka SudBiju ViswanathPublished in: Disease models & mechanisms (2022)
Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD) in comparison with healthy controls. The BD patients also had morphological brain abnormalities evident on magnetic resonance imaging. Time-lapse analysis of migrating cells was performed, through which we were able to identify several parameters that were abnormal in cellular migration, including the speed and directionality of NPCs. We also performed transcriptomic analysis to probe the mechanisms behind the aberrant cellular phenotype identified. Our analysis showed the downregulation of a network of genes, centering on EGF/ERBB proteins. The present findings indicate that collective, systemic dysregulation may produce the aberrant cellular phenotype, which could contribute to the functional and structural changes in the brain reported for bipolar disorder. This article has an associated First Person interview with the first author of the paper.
Keyphrases
- bipolar disorder
- induced apoptosis
- cell cycle arrest
- magnetic resonance imaging
- major depressive disorder
- resting state
- white matter
- signaling pathway
- endoplasmic reticulum stress
- functional connectivity
- cell proliferation
- cell death
- early onset
- machine learning
- oxidative stress
- multiple sclerosis
- chronic kidney disease
- endothelial cells
- prognostic factors
- pi k akt
- subarachnoid hemorrhage
- contrast enhanced
- high glucose
- patient reported outcomes