The effect of HMGB1 on sub-toxic chlorpyrifos exposure-induced neuroinflammation in amygdala of neonatal rats

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• 作者：Jing Tian^a ; Hongmei Dai^a ; Yuanying Deng^a ; Jie Zhang^b ; Ying Li^a ; Jun Zhou^a ; Mingyi Zhao^a ; Mengwen Zhao^a ; Chen Zhang^a ; Yuxi Zhang^c ; Peipei Wang^a ; Guoying Bing^d ; Lingling Zhao^a ; ^{llzhao2011@qq.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CPF ; chlorpyrifos ; SN ; substantia nigra ; HMGB1 ; high-mobility group box 1 ; NF-κB ; nuclear factor kappa B ; DMSO ; dimethyl sulfoxide ; IL-6 ; interleukin-6 ; TNF-α ; tumor necrosis factor-α
• 刊名：Toxicology
• 出版年：2015
• 出版时间：2 December 2015
• 年：2015
• 卷：338
• 期：Complete
• 页码：95-103
• 全文大小：2869 K

文摘

Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5 mg/kg CPF for 4 consecutive days (postnatal day 11–14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala.