Effect of BDNF on Mitochondrial Morphology and Protein Expression in NSC‐34 Cells

Abstract

Age related loss of larger phrenic motor neurons (PhMNs) may underlie diaphragm muscle sarcopenia. We found increased mitochondrial fragmentation in larger PhMNs, similar to that reported to be associated with motor neuron loss in amyotrophic lateral sclerosis (ALS). In rodents, we observed diminished brain‐derived neurotrophic factor (BDNF) signaling via its high affinity TrkB.FL receptor in older animals. TrkB.FL is expressed on the outer mitochondrial membrane, and in ALS models, BDNF/TrkB.FL signaling promotes motor neuron survival and mitochondrial fusion. In the present study, we hypothesized that enhancing BDNF/TrkB.FL signaling increases Mfn2 expression, thereby promoting mitochondrial fusion. Studies were conducted using a mouse motor neuron‐like cell line (NSC‐34), which were differentiated by serum depletion until neurite structures were observed. The differentiated NSC‐34 cells were treated with BDNF (12.5 ng/ml for 1 h) and then loaded with MitoTracker Green to image mitochondria using a Nikon A1R confocal microscope (60× oil immersion 1.4 NA). BDNF treatment increased both form factor and aspect ratio of mitochondria by ~ 20% and 15%, respectively, while also causing a threefold increase in expression of Mfn2, indicating mitochondrial fusion. These experiments were performed in six different trials with two replicates each. The observed relationship between BDNF/TrkB.FL signaling and mitochondrial fusion/fragmentation proteins supports our hypothesis. These results are consistent with diminished BDNF/TrkB.FL signaling underlying mitochondrial fragmentation and dysfunction in age‐related PhMN loss.Support or Funding InformationSupported by NIH grant AG44615This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.