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Leptin reduces LPS-induced A1 reactive astrocyte activation and inflammation via inhibiting p38-MAPK signaling pathway

Published:23 September 2024 DOI: 10.1002/glia.24611 PMID: 39310943
Meiqi Sun, Yiqun Song, Xiaoxuan Hu, Zixuan Zhang, Ruolan Tan, Zhenlu Cai, Xinyi Wang, Yali Fu, Hongli You, Simeng Cui, Wanting Zhao, Jing An, Xinlin Chen, Haixia Lu

Abstract

Neurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague–Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6?h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2-D1, H2-T23, and Serping 1 and secretion of pro-inflammatory cytokines IL-6 and TNF-α. The levels of phospho-p38 (pp38) and nuclear factor-κB (NF-κB) phosphor-p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS-induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte-specific genes and the secretion of pro-inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose-dependent manner. Similarly, LPS upregulated pp38, NF-κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS-induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS-induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38-MAPK signaling pathway.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Chromium picolinate 14639-25-9 C18H12CrN3O6 710 suppliers $5.00-$1398.40
Chromium picolinate 14639-25-9 C18H12CrN3O6 710 suppliers $5.00-$1398.40
Chromium picolinate 14639-25-9 C18H12CrN3O6 710 suppliers $5.00-$1398.40
Chromium picolinate 14639-25-9 C18H12CrN3O6 710 suppliers $5.00-$1398.40
SB 203580 152121-47-6 C21H16FN3OS 317 suppliers $16.00-$2151.00
SB 203580 152121-47-6 C21H16FN3OS 317 suppliers $16.00-$2151.00
SB 203580 152121-47-6 C21H16FN3OS 317 suppliers $16.00-$2151.00
SB 203580 152121-47-6 C21H16FN3OS 317 suppliers $16.00-$2151.00
Chromium picolinate 14639-25-9 - Inquiry
Chromium picolinate 14639-25-9 - Inquiry

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