Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus

BACKGROUND: Increasing environmental levels of brominated flame retardants raise concern about possible adverse effects, particularly through early developmental exposure. OBJECTIVE: The objective of this research was to investigate neturodevelopmental mechanisms underlying previously observed behavioral impairments observed after neonatal exposure to polybrominated diphenyl ethers (PBDEs). METHODS: C57Bl/6 mice received a single oral dose of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on postnatal day (PND) 10 (i.e., during the brain growth spurt). On PND 17-19, effects on synaptic plasticity, levels of postsynaptic proteins involved in long-term potentiation (LTP), and vesicular release mechanisms were studied ex vivo. We investigated possible acute in vitro effects of BDE-47 on vesicular catecholamine release and intracellular Ca2+ in rat pheochromocytorna (PC12) cells. RESULTS: Field-excitatory postsynaptic potential (f-EPSP) recordings in the hippocampal CAI area demonstrated reduced LTP after exposure to 6.8 mg (14 mu mol)/kg body weight (bw) BDE-47, whereas paired-pulse facilitation was not affected. Western blotting of proteins in the postsynaptic, triton-insoluble fraction of hippocampal tissue revealed a reduction of glutamate receptor subunits NR2B and GluR1 and autophosphorylated-active Ca2+/calmodulin-dependent protein kinase 11 (alpha CaMKII), whereas other proteins tested appeared unaffected. Amperometric recordings in chromaffin cells from mice exposed to 68 mg (140 mu mol)/kg bw BDE-47 did not reveal changes in carecholamine release parameters. Modest effects on vesicular release and intracellular Ca2+ in PC12 cells were seen following acute exposure to 20 mu M BDE-47. The combined results suggest a postsynaptic mechanism in vivo. CONCLUSION: Early neonatal exposure to a single high dose of BDE-47 causes a reduction of LTP together with changes in postsynaptic proteins involved in synaptic plasticity in the mouse hippocampus.