The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy

• DOI: 10.1186/s12974-021-02133-y
• Publication Date: 2021-05-11T14:03:28Z
• Authors: Zhicheng Zheng; Peiyu Liang; Baohua Hou; Xin Lu; Qianwen Ma; Xiaomin Yu; Song Han; Biwen Peng; Taoxiang Chen; Wanhong Liu; Jun Yin; Xiaohua He
• Keywords: Proinflammatory cytokine; Dipeptidyl peptidase; Dipeptidyl peptidase-4 inhibitor

Abstract Background Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between and epilepsy remains unknown. Methods Analysis public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for related to conversion. Anti-epileptic effect was assessed by electroencephalogram recordings immunohistochemistry kainic acid (KA)-induced mouse model epilepsy. The phenotype, morphology function were qPCR, western blotting microscopic imaging. Results Our results demonstrated DPP4 participated conversion treatment sitagliptin (a inhibitor) attenuated KA-induced promoted expression markers (Itgax Axl) both vivo microglial inflammatory vitro. With treatment, cells did not display an activation state (enlarged cell bodies). Furthermore, these exhibited complicated intersections, longer processes wider coverage parenchyma. In addition, reduced NF-κB signaling pathway inhibited iNOS , IL-1β IL-6 proinflammatory gene CD44 . Conclusion present highlight inhibitor can attenuate promote transformation. These exhibit unique morphological features, greater migration ability better surveillance capability. possible underlying mechanism is reduce suppress response mediated microglia. Thus, we propose act attractive direction research potential target