Neurotrophin-3 promotes neural functional recovery after sepsis-associated encephalopathy by inhibiting pyroptosis through autophagy activation
10.12007/j.issn.0258-4646.2025.08.003
- VernacularTitle:神经营养因子3通过激活自噬抑制焦亡促进脓毒症脑损伤后神经功能恢复
- Author:
Yan CONG
1
;
Pei WANG
;
Zhide SUN
;
Jian YU
Author Information
1. 河北省神经损伤与修复重点实验室,河北承德 067000;河北省泛血管疾病重点实验室,河北承德 067000;承德医学院附属医院急诊科,河北 承德 067000
- Publication Type:Journal Article
- Keywords:
sepsis-associated encephalopathy;
autophagy;
pyroptosis;
neurotrophin-3;
neuron;
pyroptosis activation protein
- From:
Journal of China Medical University
2025;54(8):684-689
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and mechanism of neurotrophin-3(NT-3)in promoting neurological recovery after sep-sis-associated encephalopathy(SAE).Methods Twenty-four Sprague-Dawley(SD)rats were randomly divided into the Sham,SAE,and+NT-3 groups(n=8).Neurological deficits were evaluated using a behavioral scoring system.Western blotting was performed to assess the expression levels of NT-3,S100β,caspase-1,and microtubule-associated protein 1 light chain 3B(LC3B)in brain tissues.Immuno-histochemistry(IHC)was performed to assess interleukin-1 β(IL-1β)expression level.For cellular experiments,groups included normal,lipopolysaccharide(LPS),LPS+NT-3,LPS+NT-3+3-MA(autophagy inhibitor),and LPS+NT-3+compound C(AMPK inhibitor).Western blotting was used to analyze LC3B,NLRP3,ASC,AMPK,phosphorylated AMPK(p-AMPK),mTOR,and phosphorylated mTOR(p-mTOR)expression levels.Caspase-1 expression in cells was evaluated using immunofluorescence(IF).Results NT-3 expression in septic rat brain tissues increased progressively from d1 to d2(P＜0.05).Compared with the SAE group,the SAE+NT-3 group exhibited elevated neurological scores.The expression levels of IL-1β,S100β,and caspase-1 decreased from d1 to d2,while the aurtophagy level increased from d1 to d2(all P＜0.05).In cellular models,the LPS+NT-3 group showed decreased caspase-1 expression and increased autophagy activity compared to that in the LPS group from 1 h to 3 h(P＜0.05).Compared to the LPS+NT-3 group,the LPS+NT-3+3-MA group exhibited elevated NLRP3,ASC,and caspase-1-positive cells(P＜0.05),whereas the LPS+NT-3+Compound C group exhibited reduced p-AMPK,increased p-mTOR,and attenuated autophagy(P＜0.05).Conclusion NT-3 activates autophagy through the AMPK/mTOR signaling pathway during the early phase of SAE,thereby eliminating pyroptosis-associated proteins NLRP3 and ASC to promote neurolog-ical recovery.
