Aim: 

We have previously shown that the superior cervical ganglion (SCG) of mdx mice, which lack full-length dystrophin, has 36% fewer neurons than the wild-type (WT) and that this loss occurs early after birth. Lost neurons projected to SCG muscular targets, like the iris, in which dystrophy causes rupture of smooth muscle cell membrane. Nonetheless, surviving neurons, innervating either iris or submandibular gland (SuGl), a SCG non-muscular target, underwent reduced axon defasciculation and terminal branching. Sympathetic neuron survival and target innervation are the result of a delicate balance in the amount of pro- and mature forms of NGF and in that of the two NGF receptors, TrkA and p75NTR. Therefore, we hypothesized that, in mdx mice, an imbalance in the levels of pro- vs mature NGF and of its receptors may be responsible for SCG neuron loss and altered peripheral target innervation.

Methods: 

By real-time RT-PCR and Western immunoblot, we investigated, in the SCG, iris and SuGl of wild-type and mdx mice at different postnatal dates, the expression of NGF, TrkA and p75NTR along with that of neurofilament proteins and PSA-NCAM, proteins essential for shaping axonal architecture.

Results: 

Our data show that, during early post-natal development, levels of pro-apoptotic proNGF are higher in mdx mouse iris than in wild-type, but not in SuGl. Moreover, in mdx mouse SCG the levels of NGF receptors (TrkA and p75NTR), PSA-NCAM and neurofilament proteins are lower than in the WT.

Conclusion: 

The increase in proNGF observed in the iris of mdx mice compared with the WT, along with reduced levels of NGF receptors (TrkA and p75NTR) in SCG, may be partly responsible for the loss of ganglionic neurons projecting to the iris. These alterations, combined with a reduction in PSA-NCAM and neurofilament protein levels in SCG, may also account for reduced axon defasciculation and terminal branching observed in mdx mouse SCG targets.