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Updated: Feb 16, 2026

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure
Yangsheng Chen1, Li Xu1, Heidi Q H Xie1
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose (0.1μg/(kg▪bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the differentially expressed genes. And the changes of several picked genes have been verified by real-time PCR. A total of 145 up-regulated and 64 down-regulated genes were identified. The metabolic processes, interleukin-1 secretion and production were significantly associated with the differentially expressed genes. And the genes regulated by dioxin also clustered to cholinergic synapse and long-term potentiation. Candidate biomarker genes such as egr1, gad2, gabrb3, abca1, ccr5 and pycard may be toxicological targets for dioxin. Furthermore, synaptic plasticity and neuro-immune system may be two principal affected areas by dioxin.
Insights
Low-dose dioxin exposure in rats impaired the nervous system, affecting synaptic plasticity and neuro-immune pathways. This study identified key genes and pathways involved in dioxin
Area of Science:
- Neurotoxicology
- Environmental Health
- Molecular Biology
Background:
- Cohort studies suggest dioxins and dioxin-like PCBs may cause neurological and neurodegenerative diseases.
- Limited research exists on the specific mechanisms underlying dioxin-induced neurotoxicity.
- Understanding these mechanisms is crucial for assessing health risks associated with dioxin exposure.
Purpose of the Study:
- To investigate the molecular mechanisms of low-dose dioxin exposure on the rat nervous system.
- To identify differentially expressed genes and affected biological pathways in the brain.
- To explore potential toxicological targets and affected systems for dioxin.
Main Methods:
- Microarray analysis of brain samples from SD rats exposed to low-dose dioxin for six months.
- Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Validation of selected gene expression changes using real-time PCR.
Main Results:
- Identified 145 up-regulated and 64 down-regulated genes in dioxin-exposed rat brains.
- Significantly associated pathways included metabolic processes, interleukin-1 secretion, cholinergic synapse, and long-term potentiation.
- Candidate biomarker genes (e.g., egr1, gad2, gabrb3) were identified as potential toxicological targets.
Conclusions:
- Dioxin exposure significantly alters gene expression in the rat brain, impacting key neurological functions.
- Synaptic plasticity and the neuro-immune system are principal areas affected by dioxin toxicity.
- Identified genes and pathways provide insights into dioxin's neurotoxicological mechanisms and potential biomarkers.
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