Aerobic exercise training engages cholinergic signaling to improve emphysema induced by cigarette smoke exposure in mice

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Suehiro, Camila Liyoko ; Souza, Natalia Tiemi Simokomaki ; da Silva, Emerson Batista ; Cruz, Maysa Mariana ; Laia, Roseane Martins ; Santos, Stheffany de Oliveira ; Santana-Novelli, Fernanda Paula Roncon ; de Castro, Thamyres Barros Pereira ; Lopes, Fernanda D. T. Q. S. ; Pinheiro, Nathalia Montouro ; Tiberio, Iolanda de Fatima Lopes Calvo ; Olivo, Clarice Rosa ; Alonso-Vale, Maria Isabel ; Prado, Marco Antonio Maximo ; Prado, Vania Ferreira ; Toledo-Arruda, Alessandra Choqueta de ; Prado, Carla Maximo

• Document type: Journal article
• Source: Life Sciences; v. 301, p. 9-pg., 2022-05-04.

Abstract

Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown. Aims: As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema. Main methods: Wild-type (WT) and mutant (KDHOM) mice (65-70% of reduction in VAChT levels) were exposed to cigarette smoke (30 min, 2x/day, 5x/week, 12 weeks) and submitted or not to aerobic exercise training on a treadmill (60 min/day, 5x/week, 12 weeks). Lung function and inflammation were evaluated. Key findings: Cigarette smoke reduced body mass in mice (p < 0.001) and increased alveolar diameter (p < 0.001), inflammation (p < 0.001) and collagen deposition (p < 0.01) in lung tissue. Both trained groups improved their performance in the final physical test compared to the initial test (p < 0.001). In WT mice, exercise training protected against emphysema development (p < 0.05), reduced mononuclear cells infiltrate (p < 0.001) and increased MAC-2 positive cells in lung parenchyma (p < 0.05); however, these effects were not observed in KDHOM mice. The exercise training reduced iNOS-positive cells (p < 0.001) and collagen fibers deposition (p < 0.05) in lung parenchyma of WT and KDHOM mice, although KDHOM mice showed higher levels of iNOS-positive cells. Significance: Our data suggest that the protective effects of aerobic exercise training on pulmonary emphysema are, at least in part, dependent on the integrity of the lung cholinergic signaling. (AU)

• FAPESP's process: 16/09353-1 - The effects of cholinergic deficiency induced by reduction in VAChT in pulmonary inflammation induced by cigarrete smoke
• Grantee: Emerson Batista da Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/25689-4 - Effects of cholinergic system in acute and chronic pulmonary inflammation
• Grantee: Carla Máximo Prado
• Support Opportunities: Regular Research Grants