Microglial JAK/STAT3 pathway activity directly impacts astrocyte and spinal neuron characteristics.

Abstract After peripheral nerve injury microglial reactivity change in the spinal cord is associated with an early activation of JAK/STAT3 transduction pathway whose blockade attenuates local inflammation and pain hypersensitivity. However, the consequences of microglial JAK/STAT3-mediated signaling on neighboring cells are unknown. Using an in vitro paradigm we assessed the impact of microglial JAK/STAT3 activity on functional characteristics of astrocytes and spinal cord neurons. Purified rat primary microglia was stimulated with JAK/STAT3 classical activator interleukin-6 in the presence or absence of a selective STAT3 inhibitor and rat primary astrocytes or spinal cord neurons were exposed to microglia conditioned media (CM). JAK/STAT3 activity-generated microglial CM modulated both astrocyte and neuron characteristics. Beyond inducing mRNA expression changes of various targets of interest in astrocytes and neurons, microglia CM activated JNK, STAT3 and NF-κB intracellular pathways in astrocytes and promoted their proliferation. Without modifying neuronal excitability or survival, CM affected the nerve processes morphology and distribution of the postsynaptic density protein 95, a marker of glutamatergic synaptic contacts. These findings show that JAK/STAT3 activity in microglia impacts the functional characteristics of astrocytes and neurons. This suggests its participation in spinal cord tissue plasticity and remodeling occurring after peripheral nerve injury. This article is protected by copyright. All rights reserved.