PMID- 23719929 OWN - NLM STAT- MEDLINE DCOM- 20131023 LR - 20190911 IS - 1880-3989 (Electronic) IS - 0388-1350 (Linking) VI - 38 IP - 3 DP - 2013 TI - Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death. PG - 513-21 AB - Lead is known to induce neurotoxicity, particularly in young children, and GluR2, an AMPA-type glutamate receptor subunit, plays an important role in neuronal cell survival. Therefore, we hypothesized that altered GluR2 expression plays a role in lead-induced neuronal cell death. To test this idea, we investigated the effect of exposure to 5 and 20 microM lead for 1-9 days on the viability and GluR2 expression of primary-cultured rat cortical neurons. The number of trypan-blue stained cells was increased by exposure to 5 microM lead for 9 days or 20 microM lead for 7-9 days, and LDH release was increased after exposure to 20 microM lead for 9 days. GluR2 expression was reduced by exposure to 5-100 microM lead, but not 0.1-1 microM lead, for 9 days. Immunocytochemistry also confirmed that GluR2 expression was decreased in the presence of lead. Application of 50 ng/ml brain-derived neurotrophic factor (BDNF) led to a recovery of lead-induced neuronal cell death, accompanied with increased GluR2 expression. Our results suggest that long-term exposure to lead induces neuronal cell death, in association with a decrease of GluR2 expression. FAU - Ishida, Keishi AU - Ishida K AD - Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan. FAU - Kotake, Yaichiro AU - Kotake Y FAU - Miyara, Masatsugu AU - Miyara M FAU - Aoki, Kaori AU - Aoki K FAU - Sanoh, Seigo AU - Sanoh S FAU - Kanda, Yasunari AU - Kanda Y FAU - Ohta, Shigeru AU - Ohta S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - J Toxicol Sci JT - The Journal of toxicological sciences JID - 7805798 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, AMPA) RN - 2P299V784P (Lead) RN - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Death/drug effects/genetics MH - Cell Survival/drug effects/genetics MH - Cells, Cultured MH - Cerebral Cortex/*cytology MH - Dose-Response Relationship, Drug MH - Down-Regulation/*drug effects MH - Gene Expression/*drug effects/*genetics MH - Lead/*toxicity MH - Neurons/*drug effects/*metabolism/pathology MH - Rats MH - Rats, Wistar MH - Receptors, AMPA/*genetics/*metabolism/physiology MH - Time Factors EDAT- 2013/05/31 06:00 MHDA- 2013/10/24 06:00 CRDT- 2013/05/31 06:00 PHST- 2013/05/31 06:00 [entrez] PHST- 2013/05/31 06:00 [pubmed] PHST- 2013/10/24 06:00 [medline] AID - DN/JST.JSTAGE/jts/38.513 [pii] AID - 10.2131/jts.38.513 [doi] PST - ppublish SO - J Toxicol Sci. 2013;38(3):513-21. doi: 10.2131/jts.38.513.