Journal
ACS CHEMICAL NEUROSCIENCE
Volume 12, Issue 2, Pages 311-322Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00612
Keywords
DEHP; hippocampus; synapse; synaptic plasticity; dendritic spine
Funding
- National Natural Science Foundation of China [81472943]
- Natural Science Foundation of Liaoning Province, China [2019JH3/10300439]
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Exposure to DEHP during pregnancy can impair hippocampal synaptic plasticity in male offspring, affecting synaptic structure and dendritic spine development, possibly through the downregulation of the Rac1/PAK/LIMK1/cofilin signaling pathway. Female offspring did not show these alterations in hippocampal structure.
Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly divided into four groups and received 0, 30, 300, 750 (mg/kg)/d DEHP by gavage from gestational day (GD) 0 to postnatal day (PN) 21. Our data showed that DEHP exposure impaired hippocampal synaptic plasticity, damaged synaptic ultrastructure, and decreased synaptic protein levels in male pups. Furthermore, DEHP decreased the density of dendritic spines, affected F-actin polymerization, and downregulated the Rac1/PAK/LIMK1/cofilin signaling pathway in male offspring. However, the alterations in the hippocampi of female offspring were not observed. These results illustrate that maternal DEHP exposure could impair hippocampal synaptic plasticity by affecting synaptic structure and dendritic spine development in male offspring, which may be attributed to altered cytoskeleton construction induced by downregulation of the Rac1 /PAK/LIMK1/cofilin signaling pathway.
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