The neglected aspect of Duchenne Muscular Dystrophy (DMD): motor neurons, peripheral axon myelination and neuromuscular junctions in adult and young wild type and dystrophic mice

Proponente Maria Egle De Stefano - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Tamara Diamanti Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca
Andrea Mele Componenti strutturati del gruppo di ricerca
Antonella De Jaco Componenti strutturati del gruppo di ricerca
Componente Qualifica Struttura Categoria
Chiara Mozzetta Ricercatore Istituto di Biologia e Patologia Molecolari, CNR Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca

Duchenne muscular dystrophy (DMD) is a severe x-linked myodegenerative disease caused by defective expression of the full-length dystrophin (Dp427), a large cortical cytoskeletal protein. A few studies from our laboratory described significant retrograde effects of muscle degeneration on peripheral autonomic innervation, as well as a direct impact of the lack of dystrophin on axonal dynamics in vivo and in vitro (!-3). However, little or none has been reported on the specific outcome that this disease has on motor neurons (MNs) innervating limb muscles (among the most severely affected) and on the crosstalk that their axons establish with Schwann cells (SCs), neither in DMD patients nor in animal models (e.g. mdx mice). This aspect is of particular importance as the impact that lack of Dp427 and other dystrophins on the nervous system begins during embryonic development, in some respect framing DMD among neurodevelopmental diseases.
The main goal of this project is to begin a first analysis of the biomolecular mechanisms and intracellular pathways that are potentially altered in MNs and peripheral nerves in severe muscular pathologies, as the DMD. Particular attention will be paid to the repercussions that neuromuscular alterations have on intraspinal MN connectivity, axon growth, myelination, and regenerative capacities. The study will be conducted on the mdx mouse, a well-known experimental model of DMD, and their wild type.

LS5_3, LS5_1, LS3_1

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