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Microglial Janus kinase/signal transduction and activator of transcription 3 pathway activity directly impacts astrocyte and spinal neuron characteristics

2015; Wiley; Volume: 136; Issue: 1 Linguagem: Inglês

10.1111/jnc.13375

1471-4159

Jenny Molet, A. Mauborgne, Mickaël Diallo, Vincent Armand, David Gény, Luis Villanueva, Yves Boucher, Michel Pohl,

Neurogenesis and neuroplasticity mechanisms

Abstract After peripheral nerve injury microglial reactivity change in the spinal cord is associated with an early activation of Janus kinase ( JAK )/ STAT 3 transduction pathway whose blockade attenuates local inflammation and pain hypersensitivity. However, the consequences of microglial JAK / STAT 3‐mediated signaling on neighboring cells are unknown. Using an in vitro paradigm we assessed the impact of microglial JAK / STAT 3 activity on functional characteristics of astrocytes and spinal cord neurons. Purified rat primary microglia was stimulated with JAK / STAT 3 classical activator interleukin‐6 in the presence or absence of a selective STAT 3 inhibitor and rat primary astrocytes or spinal cord neurons were exposed to microglia conditioned media ( CM ). JAK / STAT 3 activity‐generated microglial CM modulated both astrocyte and neuron characteristics. Beyond inducing mRNA expression changes in various targets of interest in astrocytes and neurons, microglia CM activated c‐Jun N ‐terminal kinase, STAT 3 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 post‐synaptic density protein 95, a marker of glutamatergic synaptic contacts. These findings show that JAK / STAT 3 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. image We show that the activity of JAK/STAT3 pathway in microglial cells confers them a specific signaling modality toward neighboring cells, promoting astrocyte proliferation and changes in neuronal morphology. These in vitro data suggest that the early JAK/STAT3 activation in spinal cord microglia, associated with peripheral nerve injury, participates in functional alteration of various cell populations and in spinal tissue remodeling.