Lack of dystrophin leads to the selective loss of superior cervical ganglion neurons projecting to muscular targets in genetically dystrophic mdx mice.
Autonomic imbalance is a pathological aspect of Duchenne muscular dystrophy. Here, we show that the sympathetic superior cervical ganglion (SCG) of mdx mice, which lack dystrophin (Dp427), has 36% fewer neurons than that of wild-type animals. Cell loss occurs around P10 and affects those neurons innervating muscular targets (heart and iris), which, differently from the submandibular gland (non-muscular target), are precociously damaged by the lack of Dp427. In addition, although we reveal altered axonal defasciculation in the submandibular gland and reduced terminal sprouting in all SCG target organs, poor adrenergic innervation is observed only in the heart and iris. These alterations, detected as early as P5, when neuronal loss has not yet occurred, suggest that in mdx mice the absence of Dp427 directly impairs the axonal growth and terminal sprouting of sympathetic neurons. However, when these intrinsic alterations combine with structural and/or functional damages of muscular targets, neuronal death occurs.
De Stefano
M Egle
ME
Dipartimento di Biologia Cellulare e dello Sviluppo, Università La Sapienza, Piazzale Aldo Moro 5, 00185 Roma, Italy. egle.destefano@uniroma1.it
Leone
Lucia
L
Lombardi
Loredana
L
Paggi
Paola
P
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency*; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006321:Heart / Q000254:growth & development / Q000294:innervation*; D007498:Iris / Q000254:growth & development / Q000294:innervation* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D046529:Microscopy, Electron, Transmission; D009130:Muscle, Smooth / Q000294:innervation / Q000503:physiopathology; D009132:Muscles / Q000294:innervation* / Q000648:ultrastructure; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017783:Superior Cervical Ganglion / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D016189:Dystrophin