NKCC1 Activation Is Required for Myelinated Sensory Neurons Regeneration through JNK-Dependent Pathway

Autor: Xavier Navarro, Daniel Assis Santos, Laura Mòdol, Francisco González-Pérez, Stefano Cobianchi, Victor Lopezalvarez
Rok vydání: 2015
Předmět:
Zdroj: The Journal of Neuroscience. 35:7414-7427
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.4079-14.2015
Popis: After peripheral nerve injury, axons are able to regenerate, although specific sensory reinnervation and functional recovery are usually worse for large myelinated than for small sensory axons. The mechanisms that mediate the regeneration of different sensory neuron subpopulations are poorly known. The Na+-K+-Cl−cotransporter 1 (NKCC1) is particularly relevant in setting the intracellular chloride concentration. After axotomy, increased NKCC1 phosphorylation has been reported to be important for neurite outgrowth of sensory neurons; however, the mechanisms underlying its effects are still unknown. In the present study we usedin vitroandin vivomodels to assess the differential effects of blocking NKCC1 activity on the regeneration of different types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the rat. We observed that blocking NKCC1 activity by bumetanide administration induces a selective effect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neurons. To further study the mechanism underlying NKCC1 effects, we also assessed the changes in mitogen-activated protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1 activityin vitroandinvivo modified pJNK1/2/3 expression in DRG neurons. Together, our study identifies a mechanism selectively contributing to myelinated axon regeneration, and point out the role of Cl−modulation in DRG neuron regeneration and in the activation of MAPKs, particularly those belonging to the JNK family.
Databáze: OpenAIRE