Overexpression of Zinc-α2-glycoprotein Suppressed Seizures and Seizure-related Neuroflammation in Pentylenetetrazol-kindled Rats

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2018 Mar 24

PMID 29566716

Citations 16

Authors

Ying Liu

Teng Wang

Xi Liu

Yuetao Wen

Tao Xu

Xinyuan Yu

Xin Wei

Xueying Ding

Lijuan Mo

Maojia Yin

Xinjie Tan

Lifen Chen

Affiliations

Soon will be listed here.

Abstract

Background: Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFβ and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation.

Methods: We overexpressed AZGP1 in the hippocampus of rats via adeno-associated virus vector injection and observed their seizure behavior and EEG after pentylenetetrazol (PTZ) kindling. The level of typical inflammation mediators including TNFα, IL-6, TGFβ, ERK, and ERK phosphorylation were determined.

Results: The overexpression of AZGP1 reduced the seizure severity, prolonged the latency of kindling, and alleviated epileptiform discharges in EEG changes induced by PTZ. Overexpression of AZGP1 also suppressed the expression of TNFα, IL-6, TGFβ, and ERK phosphorylaton in PTZ-kindled rats.

Conclusions: ZAG may inhibit TGFβ-mediated ERK phosphorylation and inhibit neuroinflammation mediated by TNFα and IL-6, suggesting ZAG may suppress seizure via inhibiting neuroinflammation. ZAG may be a potential and novel therapeutic target for epilepsy.

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