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Pigna E, Sanna K, Coletti D, et al. Increasing autophagy does not affect neurogenic muscle atrophy. Eur J Transl Myol. 2018;28(3):7687doi: 10.4081/ejtm.2018.7687.
Pigna, E., Sanna, K., Coletti, D., Li, Z., Parlakian, A., Adamo, S., & Moresi, V. (2018). Increasing autophagy does not affect neurogenic muscle atrophy. European journal of translational myology, 28(3), 7687. https://doi.org/10.4081/ejtm.2018.7687
Pigna, Eva, et al. "Increasing autophagy does not affect neurogenic muscle atrophy." European journal of translational myology vol. 28,3 (2018): 7687. doi: https://doi.org/10.4081/ejtm.2018.7687
Pigna E, Sanna K, Coletti D, Li Z, Parlakian A, Adamo S, Moresi V. Increasing autophagy does not affect neurogenic muscle atrophy. Eur J Transl Myol. 2018 Aug 23;28(3):7687. doi: 10.4081/ejtm.2018.7687. eCollection 2018 Jul 10. PMID: 30344980; PMCID: PMC6176397.
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Eur J Transl Myol. 2018 Aug 23;28(3):7687. doi: 10.4081/ejtm.2018.7687. eCollection 2018 Jul 10.

Increasing autophagy does not affect neurogenic muscle atrophy.

European journal of translational myology

Eva Pigna, Krizia Sanna, Dario Coletti, Zhenlin Li, Ara Parlakian, Sergio Adamo, Viviana Moresi

Affiliations

  1. Department of Anatomy, Histology, Forensic Medicine & Orthopedics, Histology & Medical Embryology Section, Sapienza University of Rome, Italy.
  2. Interuniversity Institute of Myology, Italy.
  3. Sorbonne Université, CNRS UMR 8256-INSERM ERL U1164, IBPS B2A Department of Biological Adaptation and Aging, Paris, France.

PMID: 30344980 PMCID: PMC6176397 DOI: 10.4081/ejtm.2018.7687

Abstract

Physiological autophagy plays a crucial role in the regulation of muscle mass and metabolism, while the excessive induction or the inhibition of the autophagic flux contributes to the progression of several diseases. Autophagy can be activated by different stimuli, including cancer, exercise, caloric restriction and denervation. The latter leads to muscle atrophy through the activation of catabolic pathways, i.e. the ubiquitin-proteasome system and autophagy. However, the kinetics of autophagy activation and the upstream molecular pathways in denervated skeletal muscle have not been reported yet. In this study, we characterized the kinetics of autophagic induction, quickly triggered by denervation, and report the Akt/mTOR axis activation. Besides, with the aim to assess the relative contribution of autophagy in neurogenic muscle atrophy, we triggered autophagy with different stimuli along with denervation, and observed that four week-long autophagic induction, by either intermitted fasting or rapamycin treatment, did not significantly affect muscle mass loss. We conclude that: i) autophagy does not play a major role in inducing muscle loss following denervation; ii) nonetheless, autophagy may have a regulatory role in denervation induced muscle atrophy, since it is significantly upregulated as early as eight hours after denervation; iii) Akt/mTOR axis, AMPK and FoxO3a are activated consistently with the progression of muscle atrophy, further highlighting the complexity of the signaling response to the atrophying stimulus deriving from denervation.

Keywords: Autophagy; Denervation; Intermittent fasting; Neurogenic muscle atrophy; Rapamycin

Conflict of interest statement

Conflict of Interest: All authors declare no conflicts of interests.

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