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Cu(OH)2 nanopesticide induced adolescent social behavior deficits via long noncoding RNA-mediated synaptic network
Zhihua Ren1, Yonghui Duan1, Mengyao Ren1
1Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China.
Copper hydroxide (Cu(OH)₂) nanopesticides disrupt adolescent brain development, causing behavioral issues and altering synaptic function. This neurotoxicity is linked to copper imbalance and epigenetic changes.
Area of Science:
- Environmental Science
- Neuroscience
- Toxicology
Background:
- Copper hydroxide (Cu(OH)₂) nanopesticides are widely used in agriculture.
- Concerns exist regarding their neurotoxicity, environmental persistence, and bioaccumulation.
- Adolescence is a critical period for neurodevelopment, making it vulnerable to toxic exposures.
Purpose of the Study:
- To investigate the neurodevelopmental effects of subchronic oral Cu(OH)₂ nanopesticide exposure in adolescent mice.
- To elucidate the molecular mechanisms underlying Cu(OH)₂ nanopesticide-induced neurotoxicity.
Main Methods:
- Adolescent C57BL/6 mice were administered Cu(OH)₂ nanopesticides or vehicle control orally for 30 days.
- Behavioral tests assessed social interaction and novelty-seeking.
- Synaptic molecular signatures, neurotransmission, copper homeostasis, and epigenetic modifications were analyzed.
Main Results:
- Cu(OH)₂ nanopesticide exposure impaired social interaction and novelty-seeking behaviors.
- Observed neurodevelopmental deficits were associated with disrupted copper homeostasis and induced cuproptosis.
- Epigenetic reprogramming of Kdm1a via lncRNAs Shank1-204 and Acsl1-206 was identified as a key mechanism.
Conclusions:
- Subchronic Cu(OH)₂ nanopesticide exposure causes significant neurodevelopmental perturbations in adolescents.
- Aberrant copper homeostasis, cuproptosis, and specific epigenetic alterations drive NP-evoked neurodevelopmental deficits.
- Findings provide a foundation for assessing the neurotoxicological risks of engineered nanoparticles.
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