Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush

Abstract

Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

Sex differences in gene regulation in the dorsal root ganglion after nerve injury

“…The few existing studies of sex differences in nerve regeneration suggest that regeneration of myelinated neurons occurs more rapidly in females than males (Kovacic et al 2003;Kovacic et al 2004;Kovacic et al 2009). However, Tong and colleagues recently found no sex differences in axon regeneration of axotomized neurons (Tong et al 2015). Our findings support the latter study since after CCI no significant sex-specific transcriptional differences exist in genes known to be involved in axon regeneration and neuron projection development.…”

Behavioral characterization of neuropathic pain on the glabrous skin areas reinnervated solely by axotomy-regenerative axons after adult rat sciatic nerve crush

“…The absolute absences of global axonal reinnervation in the lateral plantar skin areas at the early days after sciatic nerve crush (Fig. 2) proved the completeness of axotomy for our sciatic nerve crush surgery as previously reported [8].…”

Differences in the Structure and Protein Expression of Femoral Nerve Branches in Rats

“…Myelin sheaths are critical for the physiological function of peripheral nerves, and enhancing remyelination improves functional recovery (Stassart et al, 2013). Tong et al (2015) found that remyelination is diverse among myelinated motor and sensory nerve fibers. In our study, the mean thickness of the myelin sheath of the medullated fibers in the muscular branch of the femoral nerve was greater than that of the cutaneous branch, indicating that there should be a different standard of the thickness of the myelin sheath to evaluate remyelination of sensory and motor nerve fibers.…”