AMPK regulates the maintenance and remodelling of the neuromuscular junction

Sean Y. Ng; Andrew I. Mikhail; Stephanie R. Mattina; Salah A. Mohammed; Shahzeb K. Khan; Eric M. Desjardins; Changhyun Lim; Stuart M. Phillips; Gregory R. Steinberg; Vladimir Ljubicic

Molecular Metabolism (Jan 2025)

AMPK regulates the maintenance and remodelling of the neuromuscular junction

Sean Y. Ng,
Andrew I. Mikhail,
Stephanie R. Mattina,
Salah A. Mohammed,
Shahzeb K. Khan,
Eric M. Desjardins,
Changhyun Lim,
Stuart M. Phillips,
Gregory R. Steinberg,
Vladimir Ljubicic

Affiliations

Sean Y. Ng: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Andrew I. Mikhail: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Stephanie R. Mattina: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Salah A. Mohammed: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Shahzeb K. Khan: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Eric M. Desjardins: Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Changhyun Lim: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Stuart M. Phillips: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Gregory R. Steinberg: Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1280 Main St. W., Hamilton, ON, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
Vladimir Ljubicic: Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada; Corresponding author. Department of Kinesiology, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Journal volume & issue: Vol. 91
p. 102066

Abstract

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Objective: The molecular mechanisms underlying the maintenance and adaptability of the neuromuscular junction (NMJ) remain poorly understood. This study aimed to investigate the role of AMP-activated protein kinase (AMPK) as a key regulator of NMJ stability and plasticity. Method: A comprehensive, multifaceted approach was employed, integrating genetic, physiological, and pharmacological methodologies to elucidate the role of skeletal muscle AMPK in modulating the neuromuscular synapse. Results: Our findings reveal an increased abundance of AMPK transcripts within the NMJ and an age-associated decline in AMPK activity and synapse-specific mitochondrial gene expression. Young mice null for skeletal muscle AMPK displayed a neuromuscular phenotype akin to aged animals. Pharmacological AMPK stimulation facilitated its localization in subsynaptic myonuclei, preceded the induction of several NMJ-related transcripts, and enhanced myotube acetylcholine receptor clustering. Exercise-induced AMPK activation in mouse muscle elicited a broad NMJ-related gene response, consistent with human exercise data. Conclusions: These findings highlight a critical role for AMPK in the maintenance and remodeling of the NMJ, highlighting its potential as a therapeutic target for age-related and neuromuscular disorders.

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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