title: Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.
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 atlama4-/-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 inlama4-/-. Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adultlama4-/-. 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.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Kah Meng
authors.initials: KM
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.|University of Queensland Centre for Clinical Research, The University of Queensland, Herston, Queensland 4029, Australia.
authors.forename: Kirat K
authors.initials: KK
authors.lastname: Chand
authors.affiliation: Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Hammond
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Nickolas A
authors.initials: NA
authors.lastname: Lavidis
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland 4072, Australia.|Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin
keywords: aging; laminin; maintenance; neuromuscular synapse; neurotransmission; remodeling