SRF and SRF Cofactor mRNA Expression Is Differentially Regulated by BDNF Stimulation in Cortical Neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Serum response factor (SRF) is crucial for brain function, interacting with cofactors like TCF and MKL/MRTFs.
• Dysregulation of SRF and its cofactors is implicated in neurological disorders.

Purpose of the Study:

• To investigate the effect of brain-derived neurotrophic factor (BDNF) on SRF and SRF cofactor mRNA expression in primary cultured rat cortical neurons.
• To elucidate the signaling pathway involved in BDNF-mediated regulation of these factors.

Main Methods:

• Primary cultured rat cortical neurons were stimulated with BDNF.
• mRNA expression levels of SRF and its cofactors (Elk1, MKL1/MRTFA, MKL2/MRTFB) were analyzed.
• Inhibitor experiments using ERK/MAPK pathway inhibitors were conducted.

Main Results:

• BDNF transiently induced SRF mRNA expression.
• MKL2/MRTFB mRNA expression was transiently decreased by BDNF, while Elk1 and MKL1/MRTFA remained unchanged.
• The observed alterations were primarily mediated by the extracellular signal-regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway.

Conclusions:

• BDNF reciprocally regulates SRF and MKL2/MRTFB mRNA expression through the ERK/MAPK pathway in cortical neurons.
• This regulation may fine-tune the transcription of SRF target genes.
• Findings offer insights into potential therapeutic strategies for brain diseases linked to SRF pathway alterations.