Activation of BDNF-TrkB signaling pathway-regulated brain inflammation in pentylenetetrazole-induced seizures in zebrafish

被引：34

作者：

Jin, Meng ^{[1
,2
]}

Sheng, Wenlong ^{[1
,2
]}

Han, Liwen ^{[1
,2
]}

He, Qiuxia ^{[1
,2
]}

Ji, Xiuna ^{[1
,2
]}

Liu, Kechun ^{[1
,2
]}

机构：

[1] Qilu Univ Technol, Shandong Acad Sci, Biol Inst, 28789 East Jingshi Rd, Jinan 250103, Shandong, Peoples R China

[2] Shandong Acad Sci, Key Lab Drug Screening Technol, 28789 East Jingshi Rd, Jinan 250103, Shandong, Peoples R China

来源：

FISH & SHELLFISH IMMUNOLOGY | 2018年 / 83卷

基金：

中国国家自然科学基金;

关键词：

BDNF; TrkB; Seizures; Inflammatory responses; Zebrafish; TEMPORAL-LOBE EPILEPSY; NEUROTROPHIC FACTOR BDNF; GENE-EXPRESSION; ANIMAL-MODELS; KAINIC ACID; STATUS EPILEPTICUS; MOUSE HIPPOCAMPUS; OXIDATIVE STRESS; RAT FOREBRAIN; IN-VITRO;

D O I：

10.1016/j.fsi.2018.09.010

中图分类号：

S9 [水产、渔业];

学科分类号：

0908 ;

摘要：

Seizures are sustained neuronal hyperexcitability in brain that result in loss of consciousness and injury. Understanding how the brain responds to seizures is critical to help developing new therapeutic strategies for epilepsy, a neurological disorder characterized by recurrent and unprovoked seizures. However, the mechanisms underlying seizure-dependent alterations of biological properties are poorly understood. In this study, we analyzed gene expression profiles of the zebrafish heads that were undergoing seizures and identified 1776 differentially expressed genes. Gene-regulatory network analysis revealed that BDNF-TrkB signaling pathway positively regulated brain inflammation in zebrafish during seizures. Using K252a, a TrkB inhibitor to block BDNF-TrkB signaling pathway, attenuated pentylenetetrazole (PTZ)-induced seizures, which also confirmed BDNF-TrkB mediated inflammatory responses including regulation of ill beta and nf kappa b, and neutrophil and macrophage infiltration of brain. Our results have provided novel insights into seizure-induced brain inflammation in zebrafish and anti-inflammatory related therapy for epilepsy.

引用

页码：26 / 36

页数：11

共 82 条

[41] Fit for purpose application of currently existing animal models in the discovery of novel epilepsy therapies [J].