Investigating the Role of msBDNF – TrkB Signaling in the Maintenance of Mitochondrial Populations Through the BNIP3 Mitophagy Pathway

<p>Maintenance of mitochondrial transport and clearance at the pre- and post-synaptic terminal is an essential function of neuromuscular junctions to meet their high energy demands. Damaged or dysfunctional mitochondria can put stress on these synaptic junctions, ultimately leading to the degradation of the synapse and subsequent cell death. Dysfunctional mitochondria are also often present in neuromuscular diseases such as ALS. One possible mechanism by which neurons may eliminate dysfunctional mitochondria is through the muscle-synthesized BDNF (msBDNF) /TrkB-mediated Bcl-2 nineteen-kD interacting protein (BNIP3) mitophagy pathway, although the relationship is not well-defined. BNIP3 localizes to the mitochondria and triggers a loss of membrane potential leading to mitochondrial destruction. Using a murine model, functional and dysfunctional mitochondrial populations were labelled in the gastrocnemius of control, heterozygous and homozygous muscle-synthesized BDNF knockout mice. Injections of the mitochondria-labeling dye MitoTracker were performed on 52-day-old and 87-day-old mice in order to determine if abnormalities in mitochondrial clearance are a cause of the pathophysiology observed in this model, or possibly a byproduct of it. A BNIP3-specific antibody was used to specifically label dysfunctional mitochondria at the post-synapse of these mice. The goal was to assess the relationship between the lack of msBDNF-TrkB signaling in mice and the presence of BNIP3. Finally, BNIP3 expression and the ratio of functional and dysfunctional mitochondria in gastrocnemius muscle of both control and msBDNF knockout mice was measured to determine if there is a relationship between msBDNF expression and the number of dysfunctional mitochondria at the post-synapse of the neuromuscular junction.</p>

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2025

Author dc:creator

• Horton, Jack A

Contributors dc:contributor

• Robert Belton

• BDNF
• BNIP3
• Mitochondria
• Neuromuscular Junction
• Molecular and Cellular Neuroscience
• Neuroscience and Neurobiology

Repository record dc:identifier

https://commons.nmu.edu/theses/897

OAI identifier oai:identifier

oai:commons.nmu.edu:theses-1957