Dystrophin (Dp427) is a cortical cytoskeletal protein defective in muscles and brain of Duchenne muscular dystrophy patients and of genetically dystrophic mdx mice. We previously demonstrated that superior cervical ganglion (SCG) neurons of mdx mice exhibit altered axonal growth, defasciculation and terminal branching, along with reduced nerve growth factor (NGF) receptor (TrkA and p75NTR) expressions, respect to the wild-type (WT). To investigate whether these alterations could be ascribed to a reduction in the sensitivity to NGF, SCG neurons from WT and mdx mice were cultured in the presence 10 ng/ml of NGF. After 5 h in culture, neurite length and number of principal neurites were significantly lower in mdx mouse neurons compared to the WT, while branching frequency was not affected. Phase-contrast live imaging from 3 to 16 h of culture, revealed that neurites of mdx mouse neurons spent significantly more time in retracting and pausing and less time in growing respect to the WT, with no difference in growth and retraction velocities. As Dp427 is involved in the linkage between cytoskeleton and extracellular matrix, as well as stabilization of membrane receptors, our data suggest that its lack significantly impairs signal transduction from the extracellular to the intracellular enviroment, possibly affecting cytoskeleton dynamics responsible for neurite growth.

Funds: 

Fondazione San Paolo, ASI, MIUR