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Updated: Jan 24, 2026
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Fast Micro-iontophoresis of Glutamate and GABA: A Useful Tool to Investigate Synaptic Integration
Published on: July 31, 2013
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Arsenic Trioxide Underpins Delayed Neuroinflammation and Impaired Synaptic Integrity involving Integrative Stress
Biorxiv : the Preprint Server for Biology
|January 23, 2026
Summary
Acute arsenic trioxide (ATO) exposure triggers integrated stress response (ISR) and DNA damage, leading to delayed neurotoxicity and cognitive deficits. ISR inhibitors show therapeutic potential for mitigating these effects.
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Arsenic trioxide (ATO) is an environmental toxin linked to delayed neurotoxicity after acute exposure.
- The molecular mechanisms underlying ATO-induced long-term neurodegeneration are not fully understood.
Purpose of the Study:
- To investigate the molecular pathways driving delayed neurotoxicity following acute arsenic trioxide exposure.
- To explore the therapeutic potential of integrated stress response (ISR) inhibition.
Main Methods:
- Utilized human iPSC-derived neurons and an in vivo mouse model (C57BL/6J).
- Administered a single high dose of ATO and assessed neurobehavioral and molecular changes.
- Analyzed ISR signaling (PERK, eIF2α, CHOP, ATF4), transcriptomic profiles (RNAseq), DNA damage, and immune responses (STING).
- Tested ISR inhibition using ISRIB in mouse hippocampal cells.
Main Results:
- Acute ATO exposure induced ISR signaling and cognitive deficits in mice four weeks post-exposure.
- Elevated ISR activity, DNA damage, and dysregulated STING-mediated immunity were observed in ATO-treated mouse brains.
- ISR inhibition with ISRIB mitigated ISR activation and preserved synaptic integrity.
Conclusions:
- Integrated stress response (ISR) activation and DNA damage-induced immune dysregulation are key drivers of ATO-induced delayed neurotoxicity.
- ISR inhibitors represent a promising therapeutic strategy for mitigating arsenic trioxide-related neurotoxic effects.
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