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Doctoral thesis
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Understanding the maintenance of neuromuscular integrity: role of CtBP1 and EZH2 in skeletal muscle response to denervation

Number of pages206
Imprimatur date2023-11-29
Defense date2023-11-29
Abstract

Loss of functional innervation of skeletal muscles is key in several pathologies, including sarcopenia. Neuromuscular junctions (NMJs) maintenance involves local expression of synaptic genes restricted to sub-synaptic nuclei, and a proper response to spontaneous denervation to re-innervate and preserve muscle functions. We hypothesized that the Akt/mTORC1 signaling pathway acts as a regulatory platform coordinating muscle responses to denervation. During my PhD, I characterized the expression pattern of two candidate targets, C-terminal binding protein 1 (CtBP1) and enhancer of zeste homolog 2 (EZH2) in both innervated and denervated conditions. I also studied the consequences of knocking down and/or overexpressing CtBP1 or EZH2 on synaptic gene expression, NMJ maintenance, muscle histology and metabolism. Lastly, I evaluated the role of Akt/mTORC1 in the regulation of CtBP1 and EZH2 in skeletal muscle, by comparing their expression pattern in control and TSCmKO mice, characterized by Akt/mTORC1 deregulation and used as a model for sarcopenia.

eng
Keywords
  • Skeletal muscle
  • NMJ
  • Denervation
  • CtBP1
  • EZH2
Citation (ISO format)
CATTANEO, Olivia Simone Allegra. Understanding the maintenance of neuromuscular integrity: role of CtBP1 and EZH2 in skeletal muscle response to denervation. 2023. doi: 10.13097/archive-ouverte/unige:174092
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