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

Lee, Kah Meng, Chand, Kirat K., Hammond, Luke A., Lavidis, Nickolas A. and Noakes , Peter G. (2017) Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression. Aging, 9 3: 880-899. doi:10.18632/aging.101198


Author Lee, Kah Meng
Chand, Kirat K.
Hammond, Luke A.
Lavidis, Nickolas A.
Noakes , Peter G.
Title Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression
Journal name Aging   Check publisher's open access policy
ISSN 1945-4589
Publication date 2017-03-01
Sub-type Article (original research)
DOI 10.18632/aging.101198
Open Access Status Not yet assessed
Volume 9
Issue 3
Start page 880
End page 899
Total pages 20
Place of publication Albany, NY, United States
Publisher Impact Journals LLC
Collection year 2018
Language eng
Formatted 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-a4 deficient mice (lama4-/-). The present study further investigated the role of laminin-a4 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 wildtypes 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-a4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-a4 in maintenance of the NMJ during aging.
Keyword Aging
Laminin
Maintenance
Neuromuscular synapse
Neurotransmission
Remodeling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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