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 neurodevelopmental 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 PND17-19, 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 Ca(2+) in rat pheochromocytoma (PC12) cells.


RESULTS
Field-excitatory postsynaptic potential (f-EPSP) recordings in the hippocampal CA1 area demonstrated reduced LTP after exposure to 6.8 mg (14 micromol)/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 Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII), whereas other proteins tested appeared unaffected. Amperometric recordings in chromaffin cells from mice exposed to 68 mg (140 micromol)/kg bw BDE-47 did not reveal changes in catecholamine release parameters. Modest effects on vesicular release and intracellular Ca(2+) in PC12 cells were seen following acute exposure to 20 microM BDE-47. The combined results suggest a post-synaptic mechanism in vivo.


CONCLUSIONS
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.
Dingemans
Milou M L
MM
Toxicology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands. M.Dingemans@iras.uu.nl
Ramakers
Geert M J
GM
Gardoni
Fabrizio
F
van Kleef
Regina G D M
RG
Bergman
Ake
A
Di Luca
Monica
M
van den Berg
Martin
M
Westerink
Remco H S
RH
Vijverberg
Henk P M
HP
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005411:Flame Retardants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016716:PC12 Cells; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D009419:Nerve Tissue Proteins; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether