Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity

Kaori Masai, Keita Kuroda, Nami Isooka, Ryo Kikuoka, Shinki Murakami, Sunao Kamimai, Dengli Wang, Keyue Liu, Ikuko Miyazaki, Masahiro Nishibori, Masato Asanuma

Research output: Contribution to journalArticlepeer-review

Abstract

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 × 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.

Original languageEnglish
Pages (from-to)1511-1523
Number of pages13
JournalNeurotoxicity Research
Volume39
Issue number5
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Dopamine neuron
  • High mobility group box-1
  • Hyperthermia
  • Inflammation
  • Methamphetamine
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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