RRC ID 56652
Author Fujimura M, Usuki F, Cheng J, Zhao W.
Title Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum.
Journal Toxicol. Appl. Pharmacol.
Abstract Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum.
Volume 298
Pages 1-8
Published 2016-5-1
DOI 10.1016/j.taap.2016.03.002
PII S0041-008X(16)30048-5
PMID 26965727
MeSH Animals Blotting, Western Cerebellum / drug effects* Cerebellum / growth & development Cerebellum / metabolism Cerebellum / pathology Dose-Response Relationship, Drug Down-Regulation Environmental Pollutants / toxicity* Female Male Methylmercury Compounds / toxicity* Neurites / drug effects* Neurites / pathology PC12 Cells Peptide Elongation Factor 1 / genetics* Pregnancy Prenatal Exposure Delayed Effects / chemically induced* Prenatal Exposure Delayed Effects / metabolism Prenatal Exposure Delayed Effects / pathology Rats Rats, Wistar Receptor, trkA / antagonists & inhibitors* Synapses / drug effects* Synapses / genetics
IF 3.585
Human and Animal Cells PC-12(RCB0009)