Neurotoxicity and inflammation induction in the early life stage of zebrafish in response to harmane exposure.

Authors

Lijuan Zheng, Yanling Li, Yiliang Liu, Guirong Yu, Nian Liu, Jun Zhou, Zehua Zhang, Xinyi Wu, Kaiwen Chen, Xintong Huang, Xiaozhen He

Published in

Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. Pages 110696. Sep 20, 2026. Epub Sep 20, 2026.

Abstract

Harmane is a highly lipophilic heterocyclic amine and a particularly potent tremorgenic β-carboline. This study aims to investigate the neurotoxicity of harmane and its underlying mechanisms. Zebrafish embryos at 4 h post-fertilization (hpf) were exposed to harmane. An integrated approach combining phenotypic assessment, neurodevelopmental evaluation, real-time quantitative PCR (RT-qPCR), and RNA sequencing (RNA-seq) with pathway analysis was employed. Results showed that harmane exerted dose-dependent developmental toxicity in zebrafish embryos. Specifically, continuous exposure to 2 μg/mL harmane for 120 hpf resulted in a mortality rate of nearly 50% in larvae, accompanied by various malformations including pericardial edema, yolk sac absorption disorder, abnormal head and eye development, and reduced locomotor activity. Additionally, harmane exposure was associated with alterations in dopaminergic-related neuronal signals and impairment of the central nervous system (CNS). Furthermore, RT-qPCR results showed that harmane treatment led to decreased expression of th1, th2 and dat in zebrafish, along with a significant upregulation of sncga, whereas the expression levels of sncb, syn2b, parkin, pink1 and dj1 were markedly downregulated. Moreover, RNA-seq analysis revealed transcript-level enrichment of the AGE-RAGE signaling pathway, which suggests a potential association between harmane exposure and changes in multiple Parkinson's-disease (PD) associated gene expression. Further investigation demonstrated that harmane exposure induced significant brain inflammation in larvae, with upregulated inflammation-related genes. This effect was associated with neuronal apoptosis, as indicated by acridine orange (AO) staining. This work reveals a potential correlation between harmane-triggered neuroinflammation and neuronal damage. Further dedicated work is required to clarify whether these toxic responses are relevant to human neurodegenerative disease etiology.

PMID:
42764036
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.

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