Micaela L. O'Reilly, Mariah J. Wulf, Theresa M. Connors, Ying Jin, Frank Bearoff, Julien Bouyer, Sandhya Kortagere, John R. Bethea, Veronica J. Tom
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引用次数: 0
Abstract
After high-level spinal cord injury (SCI), persistently reactive microglia drive widespread plasticity throughout the neuraxis. Plasticity in the thoracolumbar cord, a region corresponding to the spinal sympathetic reflex (SSR) circuit, contributes to the development of sympathetic dysfunction and associated immune disorders. The transcription factor NF-κB is activated after SCI, promoting a pro-inflammatory loop by driving the expression of inflammatory mediators which further activate NF-κB signaling. We hypothesize that microglial NF-κB signaling via IKKβ modulates microglial activity, impacting central and peripheral immune activity related to the SSR circuit post-SCI. We assessed the effect of deleting canonical IKKβ in CNS-resident microglia, its impact on microglial activation, polarization, central transcriptional activity, and peripheral immune activity at 1- and 4-week post-SCI (wpi). Transcriptomic analyses reveal microglial IKKβ influences immune-related pathways in the thoracolumbar cord at 1 wpi. We show that inhibition of microglial NF-κB signaling via deletion of the activator IKKβ mitigates injury-induced increases in “proinflammatory” M1 microglia in the thoracolumbar cord at 4 wpi and increases the quantity of splenocytes at 1 wpi. This study advances our understanding of how microglial IKKβ signaling shapes the neuroimmune response and a peripheral immune organ after SCI.
期刊介绍:
GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.