Muguiz 2017 J Cachexia Sarcopenia Muscle

From Bioblast
Chronic tobacco smoke exposure induces aryl hydrocarbon receptor-dependent neuromuscular junction degeneration.

Link: Open Access

Miguez K, Vuda M, Sonjak V, Elkrief D, Konokhova Y, Perez A, Rico de Souza A, Baglole CJ, Hepple RT (2017)

Event: 10th International Conference on Cachexia, Sarcopenia and Muscle Wasting

Chronic tobacco smoke (TS)-related diseases, such as cancer, cardiovascular disease and Chronic Obstructive Pulmonary Disease, are associated with common elements of skeletal muscle deterioration (fast fiber shift, erosion of oxidative capacity and atrophy) that worsen clinical outcomes, including increasing the risk of death. Although chronic TS exposure is an exacerbating factor in conditions involving neuromuscular junction degeneration, including aging and amyotrophic lateral sclerosis (ALS), there are as of yet no data addressing the impact of chronic TS exposure on the neuromuscular junction and how this relates to the muscle alterations induced by TS. Furthermore, although chronic activation of the aryl hydrocarbon receptor (AHR) is linked to neurotoxicity, and the AHR responds to multiple compounds in TS, no studies have considered the role of the AHR in mediating the adverse impact of chronic TS exposure on muscle.

In the first set of experiments, we exposed 8- month-old C57Bl6 male mice to 60 minutes of TS exposure twice daily, 5 days per week, for 16 weeks. Following the final TS exposure, we examined muscle mass, neuromuscular junction morphology by confocal microscopy, and oxidative capacity by high-resolution respirometry. In the second set of experiments, we determined whether whole body knockout of the AHR would attenuate the neuromuscular junction impact of 8 weeks of TS exposure in 3-month-old male mice.

16 weeks of TS induced mild atrophy of limb muscle that was associated with neuromuscular junction degeneration and mild erosion of oxidative capacity. Strikingly, AHR knockout completely prevented the TS-induced neuromuscular junction degeneration and reduced indices of stress in homogenates of spinal cord tissue.

Chronic TS exposure induces neuromuscular junction degeneration that is dependent upon the AHR, providing novel insights into the mechanisms by which chronic TS adversely impacts skeletal muscle.


β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: CA Montreal Hepple RT, US FL Gainesville Hepple RT


Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style, Pharmacology;toxicology 


Organism: Mouse  Tissue;cell: Skeletal muscle 



HRR: Oxygraph-2k 

Labels, 2018-01 

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