Matrix metalloproteinases, purinergic signaling, and epigenetics, hubs in the spinal neuroglial network following nerve injury.

Abstract The neuroglial network characterizes synaptic transmission and accounts for both cellular elements (neurons and glia) and neural extracellular matrix (nECM) roles. Glial cells, neuron, and nECMnetwork is strongly interconnected, in physiological and pathological conditions as shownin several neurodegenerative diseases. Purinergic activation and matrix metalloproteinases (MMPs) remodeling of the spinal cord is pivotal in maladaptive plastic changes following peripheral nerve injury (PNI). To understand how purinergic and MMPs inhibition may modulate and potentially reverse the neuroglial network failure, we used the spared nerve injury (SNI) model of the sciatic nerve. Molecular and morphological analysis of astrocytic and microglial activation, purinergic and neurotrophic receptors, Histone Deacetylase (HDAC)1, HDAC2 were analyzed to define the pathways in response to the purinergic and MMPs inhibition. The data suggest complex protein interconnections, which are not passively influenced by epigenetics but actively contribute to modify the transcriptomics machinery. The present study contributes to unveiling the spinal network consistency and ultimately encourages new paths for targeted treatments in neurological diseases with benefits of neuroprotection, plasticity, and functional recovery.