Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity
Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity
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DOI：
10.1007/s12640-021-00402-5
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发表时间：
2021-08-21
影响因子：
3.7
通讯作者：
Asanuma, Masato
中科院分区：
文献类型：
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作者：
Masai, Kaori;Kuroda, Keita;Asanuma, Masato
高迁移率族盒-1 (HMGB1) 是一种普遍存在的非组蛋白核蛋白，作为转录激活剂发挥着关键作用，其细胞外释放会引发炎症。炎症反应在甲基苯丙胺 (METH) 诱导的急性多巴胺能神经毒性中至关重要。在本研究中，我们研究了中和抗 HMGB1 单克隆抗体 (mAb) 对 METH 诱导的小鼠多巴胺能神经毒性的影响。 BALB/c 小鼠在腹腔注射 METH 之前接受单次静脉注射抗 HMGB1 mAb（4 mg/kg x 2，间隔 2 小时）。注射冰毒会引起体温过高、血浆 HMGB1 浓度增加、多巴胺能神经末梢变性、小胶质细胞积聚以及纹状体中神经元 HMGB1 的细胞外释放。静脉注射抗 HMGB1 mAb 可显着抑制这些 METH 引起的变化。相比之下，注射冰毒引起的血脑屏障破坏并未受到抑制。我们的研究结果证明了抗 HMGB1 mAb 对 METH 诱导的多巴胺能神经毒性的神经保护作用，表明 HMGB1 可能在 METH 毒性中发挥最初的重要作用。
High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation. Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg x 2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia, and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injections was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity.