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The Heart-Brain Connection in Patients with Duchenne Muscular Dystrophy

  • Claudia Bearzi
  • Roberto RizziEmail author
Reference work entry
  • 31 Downloads

Abstract

Duchenne muscular dystrophy (DMD) is a progressive form of muscular dystrophy that occurs primarily in males and though in rare cases may affect females. It is caused by mutations in the DMD gene, which result in the completely lack of the related protein dystrophin (Dp427). Absence of Dp427 causes progressive weakening and degeneration of muscles. In addition, beyond skeletal muscle, these mutations alter the respiratory and heart performances, representing the leading causes of death in these patients. Furthermore, certain neuronal populations express Dp427, whose perturbation is correlated with several neural disorders in DMD patients. Recently, it has been hypothesized that dystrophin could play a fundamental role also in the axonal growth mediated by the nerve growth factor (NGF). Indeed, different studies have shown that in a dystrophic scenario, different neural populations exhibit reduced responsiveness to NGF stimulation, compared to controls. Parameters, such as number and length of neurites, growth cone advancement, and receptor ligand responsiveness (NGF/TrkA), are significantly reduced in neurons deriving from DMD patients or dystrophin-deficient (mdx) mice, a murine dystrophic model. Remarkably, the reduced sympathetic innervation affects even more distal districts, such as the heart, disturbing electrophysiology, beating, and contraction force. A deepen analysis of the relationship between the heart and brain in the context of DMD offers a new strategy for patient stratification and knowledge of the pathology that could open up new therapeutic scenarios.

Keywords

Heart Brain Innervation Duchenne muscular dystrophy Nerve growth factor Sympathetic nervous system Fibrosis Postganglionic adrenergic neurons 

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Institute for Genetic and Biomedical Research (IRGB), National Research Council of Italy (CNR)MilanItaly
  2. 2.Fondazione Giovanni Paolo IICampobassoItaly
  3. 3.Institute of Cell Biology and Neurobiology (IBCN), National Research Council of Italy (CNR)RomeItaly
  4. 4.Fondazione Istituto Nazionale di Genetica Molecolare (INGM) “Romeo ed Enrica Invernizzi”MilanItaly

Section editors and affiliations

  • Alessia Pascale
    • 1
  • Emilia d'Elia
    • 2
  1. 1.Department of Drug Sciences, Section of PharmacologyUniversity of PaviaPaviaItaly
  2. 2.Dipartimento CardiovascolareAzienda Ospedaliera Papa Giovanni XXIIIBergamoItaly

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