First Author | Lee KM | Year | 2017 |
Journal | Aging (Albany NY) | Volume | 9 |
Issue | 3 | Pages | 880-899 |
PubMed ID | 28301326 | Mgi Jnum | J:272591 |
Mgi Id | MGI:6285282 | Doi | 10.18632/aging.101198 |
Citation | Lee KM, et al. (2017) Functional decline at the aging neuromuscular junction is associated with altered laminin-alpha4 expression. Aging (Albany NY) 9(3):880-899 |
abstractText | Laminin-alpha4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-alpha4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-alpha4 deficient mice (lama4(-/-)). The present study further investigated the role of laminin-alpha4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-alpha4, 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-alpha4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-alpha4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-alpha4 in maintenance of the NMJ during aging. |