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  • Title: Htr2b Promotes M1 Microglia Polarization and Neuroinflammation after Spinal Cord Injury via Inhibition of Neuregulin-1/ErbB Signaling.
    Author: Chen W, Gao X, Yang W, Xiao X, Pan X, Li H.
    Journal: Mol Neurobiol; 2024 Mar; 61(3):1643-1654. PubMed ID: 37747614.
    Abstract:
    The secondary injury of spinal cord injury (SCI) is dominated by neuroinflammation, which was caused by microglia M1 polarization. This study aimed to investigate the role and mechanism of Htr2b on neuroinflammation of SCI. The BV2 and HMC3 microglia were treated with lipopolysaccharide (LPS) or interferon (IFN)-γ to simulate in vitro models of SCI. Sprague-Dawley rats were subjected to the T10 laminectomy to induce animal model of SCI. Htr2b mRNA expression was measured by qRT-PCR. The expression of Htr2b and Iba-1 was detected by western blot and immunofluorescence. The expression of inflammatory cytokines in vitro and in vivo was also measured. Kyoto Encyclopedia of Genes and Genomes (KEGG) was employed to analyze Htr2b-regulated signaling pathways. Rat behavior was analyzed by the Basso, Beattie, and Bresnahan (BBB) and inclined plane test. Rat dorsal horn tissues were stained by hematoxylin-eosin (H&E) and Nissl to measure neuron loss. Htr2b was highly expressed in LPS- and IFN-γ-treated microglia and SCI rats. SCI modeling promoted M1 microglia polarization and increased levels of inflammatory cytokines. Inhibition of Htr2b by Htr2b shRNA or RS-127445 reduced the expression of Htr2b, Iba-1, and iNOS and suppressed cytokine levels. KEGG showed that Htr2b inhibited ErbB signaling pathway. Inhibition of Htr2b increased protein expression of neuregulin-1 (Nrg-1) and p-ErbB4. Inhibition of the ErbB signaling pathway markedly reversed the effect of Htr2b shRNA on M1 microglia polarization and inflammatory cytokines. Htr2b promotes M1 microglia polarization and neuroinflammation after SCI by inhibiting Nrg-1/ErbB signaling pathway.
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