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

doi:10.1016/j.molmet.2024.102066

AMPK regulates the maintenance and remodelling of the neuromuscular junction

Mol Metab. 2024 Nov 19:102066. doi: 10.1016/j.molmet.2024.102066. Online ahead of print.

Affiliations

¹ Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada.
² 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.
³ Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON, Canada. Electronic address: ljubicic@mcmaster.ca.

PMID: 39571900
DOI: 10.1016/j.molmet.2024.102066

Abstract

The neuromuscular junction (NMJ) is an electrochemical signaling apparatus essential for facilitating muscle contraction and counteracting neurodegenerative processes associated with aging and neuromuscular disorders. Although our understanding of the molecular mechanisms that govern the maintenance and plasticity of the NMJ is limited, recent evidence suggests that AMP-activated protein kinase (AMPK) is an emerging, influential player. 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. Together, these findings highlight a role for AMPK in the maintenance and remodeling of the NMJ.

Keywords: Mitochondria; PGC-1α; acetylcholine receptors; aging; exercise.