8 and 16 weeks of Chronic Tobacco Smoke Exposure Negatively Impacts Peripheral Motor Axon and Neuromuscular Junction Morphology in the Diaphragm of Mice
Bibliographic record
Abstract
Introduction Globally, chronic tobacco smoke (TS) exposure is the leading cause of preventable disease, and is the primary risk factor for the development of the top three causes of death: chronic obstructive pulmonary disease (COPD), cardiovascular disease, and cancer. Importantly, TS‐related diseases are accompanied by similar skeletal muscle abnormalities, which contribute to poor outcomes and prognosis. Recent findings have implicated TS‐induced denervation in TS‐related locomotor muscle abnormalities. Given the important physiological role of the diaphragm, and that muscle abnormalities in tobacco smokers and people with TS‐related diseases manifest differently in the diaphragm than in locomotor muscle, the objective of this study was threefold: (1) to further assess the impact of TS exposure on the diaphragm; (2) to resolve whether the TS‐induced neuromuscular junction (NMJ) impact observed in locomotor muscle also occurs in the diaphragm; and (3) to investigate the progressive impact of TS exposure on morphological features of the motor axon and NMJ. Methods 15‐wk‐old male C57Bl/6 wild‐type mice were randomly assigned to an 8‐ or 16‐wk period of either TS or control air exposure. Body mass was weighed at the beginning and end of the exposure periods. Immediately following sacrifice, epididymal fat, spleen, and liver were harvested and weighed in mice undergoing 16‐wk exposures. Diaphragm, gastrocnemius, plantaris, soleus, TA, and EDL muscles were harvested and weighed immediately following sacrifice in all mice. The diaphragm was used to analyze the morphology of motor axons and NMJs using immunofluorescent staining and confocal microscope imaging. Results 8 and 16 weeks of TS exposure attenuated body growth (p < 0.0005). Furthermore, 8 weeks (p < 0.0001), but not 16 weeks, of TS exposure reduced muscle mass normalized to their respective controls in all muscles harvested. In the diaphragm, 8 and 16 weeks of TS exposure increased the fraction of NMJs lacking axonal input (p < 0.05) or pre‐synaptic nerve terminal structures (p < 0.005), the latter identified as denervated structures. Pre‐synaptic axon diameter was reduced following 16 (p < 0.05), but not 8, weeks of TS exposure. 8 and 16 weeks of TS exposure led to reduced compactness of AChR structures (p < 0.005), in the absence of AChR fragmentation. Conclusions Chronic TS exposure leads to reduced muscle mass of 8‐week TS‐exposed mice, as well as abnormal morphology of diaphragm motor axons and NMJs in 8‐ and 16‐wk TS‐exposed mice. Increased exposure length resulted in an exacerbation of the impact of TS on reduced pre‐synaptic axon growth and AChR compactness in 16‐wk versus 8‐wk TS exposed mice. These findings illustrate that chronic TS exposure results in specific morphological abnormalities in motor axons and NMJs in the diaphragm muscle. Support or Funding Information Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de recherche en santé du Canada): Russell T. Hepple, 119583 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".