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Cited by 133Toxic Organic Pollutants ImpactNeuroscience and Neuropharmacology ResearchEffects and risks of endocrine disrupting chemicals

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

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Dingemans, Milou M.L., Ramakers, Geert M.J., Gardoni, Fabrizio, van Kleef, Regina G.D.M., Bergman, Åke, Di Luca, Monica, van den Berg, Martin, Westerink, Remco H.S. +1 more·2007·Environmental Health Perspectives
DOI 10.1289/ehp.9860PMC PMC1892123
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Abstract

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 Ca2+ 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 μmol)/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 II (αCaMKII), whereas other proteins tested appeared unaffected. Amperometric recordings in chromaffin cells from mice exposed to 68 mg (140 μmol)/kg bw BDE-47 did not reveal changes in catecholamine release parameters. Modest effects on vesicular release and intracellular Ca2+ in PC12 cells were seen following acute exposure to 20 μM BDE-47. The combined results suggest a post-synaptic 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.

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  • In neonatal mice, TBBPA caused a small reduction in post-tetanic potentiation, while overall LTP effects remained modest, indicating that brief developmental exposure can perturb early activity-dependent synaptic strengthening.

    “In neonatal mice, TBBPA caused a small reduction in post-tetanic potentiation, although overall LTP effects remained modest, indicating that even brief developmental exposure can perturb early forms of activity-dependent synaptic strengthening (Dingemans et al., 2007; Hendriks et al., 2015).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Dingemans et al., 2007

    The Methods identify the neonatal exposure as a single dose of BDE-47, not TBBPA. The Results report significantly reduced post-tetanic potentiation and LTP in BDE-47–exposed mice. This source therefore makes a contrary point about the substance responsible for the effects. (LLM, conf=0.90)

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Authors
Dingemans, M. M. L., Ramakers, G. M. J., Gardoni, F., van Kleef, R. G. D. M., Bergman, Å., Di Luca, M., van den Berg, M., Westerink, R. H. S., & Vijverberg, H. P. M.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University Medical Center Utrecht (NL)
  • University of Milan (IT)
  • Toxicology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
  • Stockholm University (SE)
  • Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy
  • Utrecht University (NL)
Corresponding author
Dingemans, Milou M.L.
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2007-02-05
Volume
115
Issue
6
Pages
865-870
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.9860
PMC
PMC1892123
OpenAlex
W2152248981
Cited by
133
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 6 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 6
FWCI
11.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • U.S. Environmental Protection Agency (P42 ES05947)
  • U.S. Department of Veterans Affairs
  • Brigham and Women's Hospital
  • Deutsches Krebsforschungszentrum
  • Abiomed
  • Universiteit Utrecht
  • National Institutes of Health (14642, P42-ES05947, ES-00002)
  • Centers for Disease Control and Prevention
  • National Institute of Environmental Health Sciences (P 42-ES05947, P30-ES00002, ES 00002)
  • National Center on Minority Health and Health Disparities
  • National Center for Research Resources (M01 RR 02635, M01RR002635)
  • Agency for Toxic Substances and Disease Registry
  • National Institute on Minority Health and Health Disparities
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
brominated flame retardants, BDE-47, polybrominated diphenyl ethers, neonatal exposure, long-term potentiation, synaptic plasticity, hippocampus, postsynaptic proteins, NR2B, GluR1, CaMKII, glutamate receptors, catecholamine release, intracellular calcium, developmental neurotoxicity, brain growth spurt
MeSH terms
Analysis of Variance, Animals, Animals, Newborn, Flame Retardants, Gene Expression Regulation, Hippocampus, Mice, Inbred C57BL, Nerve Tissue Proteins, Polybrominated Biphenyls, Blotting, Western, PC12 Cells, Long-Term Potentiation, Mice, Rats, Halogenated Diphenyl Ethers

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