Research Paper|Volume 9, Issue 3|pp 880—899

Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression

Kah Meng Lee¹, Kirat K. Chand^1,², Luke A. Hammond³, Nickolas A. Lavidis¹, Peter G. Noakes^1,³

¹School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia
²University of Queensland Centre for Clinical Research, The University of Queensland, Herston, Queensland 4029, Australia
³Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland 4072, Australia

Received: November 21, 2016Accepted: March 3, 2017Published: March 14, 2017

Copyright: © 2017 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.