Regulation of Nurr1 and Nur77 by miR-19a-3p and miR-19b-3p during spinal cord injury

SAHEBDEL, F; H.R QUINTÁ; MORSE, L; OLSON, J; BATTAGLINO, R

Congreso; Immunology 2024; 2024

Spinal cord injury (SCI) often leads to neuropathic pain, a challenging condition affecting a significant proportion of individuals with SCI. Neuroinflammation, driven by microglia activation, has been implicated in the development of neuropathic pain. We previously conducted an miRNA screening and identified miR-19a and miR-19b as being increased in SCI patients with pain versus no pain. In these studies we wanted to determine the effect of miR-19a and miR-19 on microglia. miR-19a and miR-19b increased the expression of pro-inflammatory cytokines and decreased the expression of Nurr1 and Nurr77 in microglia stimulated with LPS or IFN. Nurr1 and Nur77 are nuclear receptors that are involved in the regulation of the pro-inflammatory response. Next, we wanted to determine the role of Nurr1 and Nurr77 in controlling the inflammatory response by microglia after SCI. Silencing Nurr1 and Nur77 expression in microglia led to an increased pro-inflammatory response. Using a SCI model in rats, Nurr1 and Nur77 expression was decreased in microglia in the central nervous system following injury correlating with increased expression of inflammatory cytokines. These results suggest that miR-19a and miR-19b are increased following SCI which decreases Nurr1 and Nur77 leading to an increased inflammatory response by microglia. The results from these studies may promote the development of treatments to regulate neuroinflammation and reduce neuropathic pain in individuals with SCI.