Related Experiment Video
Updated: Mar 27, 2026
In Vivo Forward Genetic Screen to Identify Novel Neuroprotective Genes in Drosophila melanogaster
Published on: July 11, 2019
The gene BRAF is underexpressed in bipolar subject olfactory neuroepithelial progenitor cells undergoing apoptosis
Emily Schroeder1, Yonglin Gao1, Zhenmin Lei2
1Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY, USA.
Background:
Bipolar disorder is a devastating psychiatric condition that frequently results in various degrees of brain tissue loss, cognitive decline, and premature death. The documentation of brain tissue loss implicates apoptosis as the likely underlying degenerative process, but direct experimental demonstration is lacking.
Methods:
Olfactory neuroepithelial biopsies from individuals with and without bipolar I disorder yielded olfactory neuroepithelial progenitor cells (ONPs), which spontaneously differentiate into neurons and glia. Glutamate, 0.1M, for 3 and 6h was used to induce apoptosis. Genes involved in the apoptotic pathway were interrogated with micro-array analysis before and after glutamate treatment for 6h. Confirmation was accomplished with real-time PCR. Total and phospho-B-Raf protein levels were measured using Western blot analysis.
Results:
ONPs from bipolar individuals demonstrated significantly greater apoptosis than cells from non-bipolar subjects. Microarray results revealed 12 differentially expressed genes. Five genes were further examined. BRAF mRNA and protein levels were significantly reduced in bipolar ONPs.
Conclusions:
ONPs with the genetic heritage of bipolar I disorder were more sensitive to glutamate induced apoptosis. Under expression of the BRAF gene and protein, which plays a role in regulating the pro-survival MEK/ERK signaling pathway, may contribute to this apoptotic sensitivity.
More Related Videos
08:33Olfactory Neurons Obtained through Nasal Biopsy Combined with Laser-Capture Microdissection: A Potential Approach to Study Treatment Response in Mental Disorders
Published on: December 4, 2014
09:24Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:30Apoptosis
01:03Olfactory Receptors: Location and Structure
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...