THE ROLE OF SKELETAL MUSCLE SYNTHESIZED BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) ON THE HEALTH AND MAINTENANCE OF THE MURINE MOTOR UNIT

<p>Skeletal muscle is a cytokine-producing organ capable of expressing various myokines, including tumor necrosis factor alpha, IL-6, IL-8, IL-15, IL-17, and brain-derived neurotrophic factor (BDNF) (Pederson, 2011, So et al., 2014, Schnyder and Handschin, 2015). BDNF is a small neurotrophic protein, that regulates neuron differentiation, maturation, and survival, and modulates central nervous system neurotransmitters (Oppenheim, 1991; Acheson et al., 1995; Binder and Scharfman, 2004; Reichardt, 2006). However, the role of BDNF in skeletal muscle health and maintenance is not well understood. To investigate this, we used a mouse model with Cre/Lox targeted gene deletion driven by the human alpha skeletal actin promoter, resulting in experimental animals with reduced or absent muscle-derived BDNF (MuscleBDNF^+/-, MuscleBDNF^-/-). We examined gastrocnemius and soleus muscles across multiple age groups (30, 90, 120, 180, and 210 days), assessing myofiber health in the absence or reduction of skeletal-derived BDNF. Significant pathology was observed in gastrocnemius tissues of both young and young-adult transgenic mice lacking endogenous BDNF, including mispositioned nuclei, split fibers, and fewer total myofibers, further histological analysis showed that fast-twitch myofibers were disproportionally affected. We next assessed the structure of gastrocnemius associated neuromuscular junctions of 120d mice and found that there is a presynaptic decrease of vesicle acetylcholine transporter and an increased probability of junction fragmentation in muscle BDNF knockout mice. Taken altogether these findings suggest that muscle-synthesized BDNF plays a role in the maintenance of muscle fibers and retrogradely affects innervating gastrocnemius associated motorneurons at 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

2019

Author dc:creator

• Taisto, Mandy E

Contributors dc:contributor

• Dr Erich Ottem

• BDNF
• Brain-Derived Neurotrophic Factor
• Neurotrophins
• Skeletal Muscle
• NMJ Remodeling
• ALS
• Biology

Repository record dc:identifier

https://commons.nmu.edu/theses/857

OAI identifier oai:identifier

oai:commons.nmu.edu:theses-1913