Date of Award
Master of Science
Erich N. Ottem
Mitochondria are essential for the high energy demands of the neuromuscular junction and, as a consequence, leave motorneurons susceptible to dysfunction. A potential origin of progressive pathology may be a reduction in brain-derived neurotrophic-factor (BDNF) signaling at the motor unit. We have shown that mice deficient in skeletal muscle-synthesized BDNF (msBDNF) demonstrate progressive motorneuron and muscle pathology at 120d. We hypothesize mitochondrial populations will be altered in motorneurons of msBDNF deficient-mice. At 117d, msBDNF deficient-mice received intramuscular injections of MitoTracker™ dye targeting the right gastrocnemius muscle. At 120d experimental groups underwent a gastrocnemius harvest or a sciatic nerve ligation protocol prior to sacrifice. In combination with MitoTracker™ injections, we used immunohistochemical labeling to target the mitochondrial translocase of outer membrane, TOM20. We used immunolabeling to further delineate mitochondrial populations within gastroc-associated motorneurons. To determine if experimental groups exhibit altered mitochondrial populations, we used confocal microscopy and IMARIS 3D rendering software. Immunolocalization was measured throughout the axon and axon terminals of motorneurons. We found no significant difference in mitochondrial populations within the pre-or post-synapse of control and msBDNF deficient animals. Results indicate that co-labeling mitochondria in a sciatic nerve ligation model illustrate mitochondrial population, as well as utility during transport. We found no significant difference in mitochondrial populations along the motor axon of msBDNF deficient mice at 120d. Ongoing studies suggest that mitochondrial populations and mobility may be as dynamic as mitochondrial function and assisted by the coexistence of several signaling mechanisms.
Cawley, Mikel, "THE ROLE OF SKELETAL MUSCLE-SYNTHESIZED BRAIN DERIVED NEUROTROPHIC FACTOR IN THE MAINTENANCE OF MOTOR NEURON MITOCHONDRIAL POPULATIONS" (2020). All NMU Master's Theses. 610.