Frontiers in Cellular Neuroscience (Feb 2015)
Peripheral nerve injury induces glial activation in primary motor cortex
Abstract
Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen), GAP-43 (growth-associated protein 43), GFAP (glial fibrillary acidic protein), and Iba 1 (Ionized calcium binding adaptor molecule 1) were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1). Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white matter, CxS1 and vM1. Additionally, immunoreactivity to Iba 1 was increased in sensorimotor cortex 3 days after lesion. Taken together these findings demonstrate that unilateral facial nerve lesions induce widespread bilateral reorganization in sensorimotor cortices encompassing transient neuronal shrinkage, axon sprouting, and astrocytic and microglia activation. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and glia interaction
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