title: Reduced TrkB expression results in precocious age-like changes in neuromuscular structure, neurotransmission, and muscle function.
abstract: Acute blockade of signaling through the tyrosine kinase receptor B (TrkB) attenuates neuromuscular transmission and fragments postsynaptic acetylcholine receptors (AChRs) in adult mice, suggesting that TrkB signaling is a key regulator of neuromuscular function. Using immunohistochemical, histological, and in vitro muscle contractile techniques, we tested the hypothesis that constitutively reduced TrkB expression would disrupt neuromuscular pre- and postsynaptic structure, neurotransmission, muscle fiber size, and muscle function in the soleus muscle of 6- to 8-mo-old TrkB⁺/⁻ mice compared with age-matched littermates. Age-like expansion of postsynaptic AChR area, AChR fragmentation, and denervation was observed in TrkB⁺/⁻ mice similar to that found in 24-mo-old wild-type mice. Neurotransmission failure was increased in TrkB⁺/⁻ mice, suggesting that these morphologic changes were sufficient to alter synaptic function. Reduced TrkB expression resulted in decreased muscle strength and fiber cross-sectional area. Immunohistochemical and muscle retrograde labeling experiments show that motor neuron number and size are unaffected in TrkB⁺/⁻ mice. These results suggest that TrkB- signaling at the neuromuscular junction plays a role in synaptic stabilization, neurotransmission, and muscle function and may impact the aging process of sarcopenia.
authors: Program in Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
authors: Scott A
authors: SA
authors: Kulakowski
authors: Sara D
authors: SD
authors: Parker
authors: Kirkwood E
authors: KE
authors: Personius
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D053580:Muscle Strength; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011950:Receptors, Cholinergic / Q000378:metabolism; D055948:Sarcopenia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission; D020813:Receptor, trkB
chemical_list: D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011505:Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB; C073922:neurotrophin 4