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.
","abstract_html":"<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<sup>+/-</sup>, MuscleBDNF<sup>-/-</sup>). 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>","abstract_has_math":false,"creators":["Taisto, Mandy E"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Biology","degree_department":null,"school":null,"contributors":["Dr Erich Ottem"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-12-01T08:00:00Z","date_published":"2019-12-01T08:00:00Z","updated_at":"2026-07-24T03:24:36Z","subjects":["BDNF","Brain-Derived Neurotrophic Factor","Neurotrophins","Skeletal Muscle","NMJ Remodeling","ALS","Biology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.nmu.edu/theses/857","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr Erich Ottem"]},{"key":"dc:creator","label":"Author","values":["Taisto, Mandy E"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2029-07-11T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["BDNF","Brain-Derived Neurotrophic Factor","Neurotrophins","Skeletal Muscle","NMJ Remodeling","ALS","Biology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.nmu.edu/theses/857"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["THE ROLE OF SKELETAL MUSCLE SYNTHESIZED BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) ON THE HEALTH AND MAINTENANCE OF THE MURINE MOTOR UNIT"]}]}],"canonical_facts":{"dc:contributor":["Dr Erich Ottem"],"dc:creator":["Taisto, Mandy E"],"dc:date.available":["2029-07-11T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://commons.nmu.edu/theses/857"],"dc:subject":["BDNF","Brain-Derived Neurotrophic Factor","Neurotrophins","Skeletal Muscle","NMJ Remodeling","ALS","Biology"],"dc:title":["THE ROLE OF SKELETAL MUSCLE SYNTHESIZED BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) ON THE HEALTH AND MAINTENANCE OF THE MURINE MOTOR UNIT"],"thesis:degree_discipline":["Biology"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T03:24:36Z"}