PUBLICATION
2-Hydroxy-4-n-octyloxybenzophenone induces developmental neurotoxicity and multiple sclerosis-like symptoms through cacna1a regulated Ca2 + inward flow and microglial activation
- Authors
- Li, X., Gao, X., Liu, S., Liu, S., Liu, Y., Gao, L., Xia, L., Liu, K., Jin, M.
- ID
- ZDB-PUB-250407-6
- Date
- 2025
- Source
- Ecotoxicology and environmental safety 295: 118154118154 (Journal)
- Registered Authors
- Keywords
- Ca(2+) inward flow, Developmental neurotoxicity, Multiple sclerosis, UV-531, cacna1a
- MeSH Terms
-
- Zebrafish
- Locomotion/drug effects
- Water Pollutants, Chemical*/toxicity
- Calcium/metabolism
- Animals, Genetically Modified
- Dopaminergic Neurons/drug effects
- Multiple Sclerosis*/chemically induced
- Sunscreening Agents*/toxicity
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Animals
- Benzophenones*/toxicity
- Neurotoxicity Syndromes*/etiology
- Microglia/drug effects
- Blood-Brain Barrier/drug effects
- PubMed
- 40188732 Full text @ Ecotoxicol. Environ. Saf.
Citation
Li, X., Gao, X., Liu, S., Liu, S., Liu, Y., Gao, L., Xia, L., Liu, K., Jin, M. (2025) 2-Hydroxy-4-n-octyloxybenzophenone induces developmental neurotoxicity and multiple sclerosis-like symptoms through cacna1a regulated Ca2 + inward flow and microglial activation. Ecotoxicology and environmental safety. 295:118154118154.
Abstract
2-Hydroxy-4-n-octyloxybenzophenone (UV-531) is a UV absorber widely used in infrastructure, cosmetics, and rubber products. The previous study found that UV-531 exposure irritate the skin and interfere with androgen secretion. However, the developmental toxicity and neurotoxic effects of UV-531 are still at an exploratory stage, and the effects of UV-531 on the environment and living organisms need to be further explored. Here, we exposed zebrafish to environmental relevant doses of UV-531 (0.1, 0.2, 0.4, 0.8 and 1.6 μg/L) and observed no significant developmental toxicity, but significant neurotoxicity. We assessed locomotor ability and responsiveness of zebrafish by general locomotion and light/dark challenge. Changes in dopaminergic (DA) neurons were observed using transgenic zebrafish slc18a2:GFP. Changes in cerebral vessels and blood-brain barrier (BBB) were observed using transgenic zebrafish fli1:GFP. Gene expression was detected by transcriptome and real-time qPCR. The effect of UV-531 on calcium homeostasis was determined by measuring Ca2+ levels. Microglia status was assessed by in situ hybridization. It was observed that UV-531 treatment resulted in a reduced locomotor activity, DA neurons injury, cerebral vessels damage, BBB leakage, calcium homeostasis imbalance, and abnormal expression of genes related to neurodevelopment and function. RNA-seq results indicated that Ca2+ import across plasma membrane was highly associated with UV-531-induced developmental neurotoxicity and cacna1aa and cacna1ab were key regulators. These findings suggest that UV-531 induced calcium homeostasis imbalance caused by upregulating cacna1aa and cacna1ab may contribute to multiple sclerosis (MS). Accordingly, UV-531 exposure triggered neuroinflammation, injured myelin, ultimately leading to the development of MS-like symptoms, including decreased responsiveness to external stimuli, microglia activation, dysregulation of mbp and MS-related genes ahsg1, btg1, and grna. In summary, exposure to environmental relevant doses of UV-531 caused neurological damage and led to MS-like symptoms. Given the effects of UV-531 on the organisms, a safe dose range should be established.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping