Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression
نویسندگان
چکیده
Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice (lama4-/-). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing. Results showed maintained perturbed transmission properties at lama4-/- NMJs from adult (3 months) through to aged (18-22 months). Hind-limb grip force demonstrated similar trends as transmission properties, with maintained weaker grip force across age groups in lama4-/-. Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adult lama4-/-. Most significantly, altered expression of laminin-α4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-α4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging.
منابع مشابه
Neural control of aging skeletal muscle.
Functional and structural decline in the neuromuscular system with aging has been recognized as a cause of impairment in physical performance and loss of independence in the elderly. Alterations in spinal cord motor neurones and at the neuromuscular junction have been identified as evidence of denervation in skeletal muscles from aging mammals, including humans. However, the reciprocal influenc...
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