CoChat
Sign Up
Cited by 45Toxic Organic Pollutants ImpactEffects and risks of endocrine disrupting chemicalsPesticide Exposure and Toxicity

Developmental Exposure to a Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats

Open access
Kodavanti, Prasada Rao S., Royland, Joyce E., Osorio, Cristina, Winnik, Witold M., Ortiz, Pedro, Lei, Lei, Ramabhadran, Ram, Alzate, Oscar·2015·Environmental Health Perspectives
DOI 10.1289/ehp.1408504PMC PMC4421769
Open this paper in CoChat — free account

Abstract

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular and molecular mechanisms for these neurotoxic effects are not fully understood; however, several studies have shown that PBDEs affect thyroid hormones, cause oxidative stress, and disrupt Ca2+-mediated signal transduction. Changes in these signal transduction pathways can lead to differential gene regulation with subsequent changes in protein expression, which can affect the development and function of the nervous system. OBJECTIVE: In this study, we examined the protein expression profiles in the rat cerebellum and hippocampus following developmental exposure to a commercial PBDE mixture, DE-71. METHODS: Pregnant Long-Evans rats were dosed perinatally with 0 or 30.6 mg/kg/day of DE-71 from gestation day 6 through sampling on postnatal day 14. Proteins from the cerebellum and hippocampus were extracted, expression differences were detected by two-dimensional difference gel electrophoresis, and proteins were identified by tandem mass spectrometry. Protein network interaction analysis was performed using Ingenuity® Pathway Analysis, and the proteins of interest were validated by Western blotting. RESULTS: Four proteins were significantly differentially expressed in the cerebellum following DE-71 exposure, whereas 70 proteins were significantly differentially expressed in the hippocampus. Of these proteins, 4 from the cerebellum and 47 from the hippocampus, identifiable by mass spectrometry, were found to have roles in mitochondrial energy metabolism, oxidative stress, apoptosis, calcium signaling, and growth of the nervous system. CONCLUSIONS: Results suggest that changes in energy metabolism and processes related to neuroplasticity and growth may be involved in the developmental neurotoxicity of PBDEs.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1289/ehp.1408504

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Decrease of synapsin I phosphorylation can enable less vesicles to be released during presynaptic depolarization.

    “which can enable less vesicles to be released during the presynaptic depolarization.34”

    From Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms (2017) · cites this paper as [34]

    The Discussion describes changes in proteins involved in synaptic signaling and vesicle trafficking, but does not address whether reduced synapsin I phosphorylation limits vesicle release during presynaptic depolarization. A References entry calls synapsin I a synaptic vesicle protein; searches for synapsin I phosphorylation and presynaptic vesicle release found no passage making the claimed connection. No page numbers are available in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 65

  1. Alaee M Arias P Sjödin A Bergman Å 2003 An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release. Environ Int 29 683 689 12850087
  2. Alban A David SO Bjorkesten L Andersson C Sloge E Lewis S 2003 A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 3 36 44 12548632
  3. Alm H Scholz B Fischer C Kultima K Viberg H Eriksson P 2006 Proteomic evaluation of neonatal exposure to 2,2’,4,4’,5-pentabromodiphenyl ether. Environ Health Perspect 114 254 259; 10.1289/ehp.8419 16451863 PMC1367840 · DOI
  4. Altman J Das GD 1965 Post-natal origin of microneurones in the rat brain. Nature 207 953 956 5886931
  5. Becker J Craig EA 1994 Heat-shock proteins as molecular chaperones. Eur J Biochem 219 11 23 8306977
  6. Bedard K Szabo E Michalak M Opas M 2005 Cellular functions of endoplasmic reticulum chaperones calreticulin, calnexin, and ERp57. Int Rev Cytol 245 91 121 16125546
  7. Beyer IW Karmali R Demeester-Mirkine N Cogan E Fuss MJ 1998 Serum creatine kinase levels in overt and subclinical hypothyroidism. Thyroid 8 1029 1031 9848718
  8. Brock TO O’Callaghan JP 1987 Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. J Neurosci 7 931 942 3106588 PMC6569013
  9. Buell SJ Fosmire GJ Ollerich DA Sandstead HH 1977 Effects of postnatal zinc deficiency on cerebellar and hippocampal development in the rat. Exp Neurol 55 199 210 849754
  10. Calabrese B Halpain S 2005 Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Neuron 48 77 90 16202710
  11. Castegna A Aksenov M Thongboonkerd V Klein JB Pierce WM Booze R 2002 Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: dihydropyrimidinase-related protein 2, α-enolase and heat shock cognate 71. J Neurochem 82 1524 1532 12354300
  12. Chaudhury A Chander P Howe PH 2010 Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: focus on hnRNP E1’s multifunctional regulatory roles. RNA 16 1449 1462 20584894 PMC2905745
  13. DeKroon RM Osorio C Robinette JB Mocanu M Winnik WM Alzate O 2011 Simultaneous detection of changes in protein expression and oxidative modification as a function of age and APOE genotype. J Proteome Res 10 1632 1644 21210719
  14. Díaz-Ramos A Roig-Borrellas A García-Melero A López-Alemany R 2012 α-Enolase, a multifunctional protein: its role on pathophysiological situations. J Biomed Biotech 2012: 156795; 10.1155/2012/156795 PMC3479624 23118496 · DOI
  15. Dingemans MM Ramakers GM Gardoni F van Kleef RG Bergman Å Di Luca M 2007 Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus. Environ Health Perspect 115 865 870; 10.1289/ehp.9860 17589592 PMC1892123 · DOI · Paper page
  16. Eaton BA Fetter RD Davis GW 2002 Dynactin is necessary for synapse stabilization. Neuron 34 729 741 12062020
  17. Erickson RR Dunning LM Olson DA Cohen SJ Davis AT Wood WG 2005 In cerebrospinal fluid ER chaperones ERP57 and calreticulin bind β-amyloid. Biochem Biophys Res Commun 332 50 57 15896298
  18. Eriksson P Fredriksson A 1996 Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse. Environ Toxicol Pharmacol 1 155 165 21781676
  19. Eriksson P Jakobsson E Fredriksson A 2001 Brominated flame retardants: a novel class of developmental neurotoxicants in our environment? Environ Health Perspect 109 903 908 11673118 PMC1240439
  20. Eskenazi B Chevrier J Rauch SA Kogut K Harley KG Johnson C 2013 In utero and childhood polybrominated dipheyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environ Health Perspect 121 257 262; 10.1289/ehp.1205597 23154064 PMC3569691 · DOI · Paper page
  21. Eun SY Kim EH Kang KS Kim HJ Jo SA Kim SJ 2006 Cell type-specific upregulation of myristoylated alanine-rich C kinase substrate and protein kinase C-α, -β I, -β II, and -δ in microglia following kainic acid-induced seizures. Exp Mol Med 38 310 319 16819290
  22. Fan CY Besas J Kodavanti PR 2010 Changes in mitogen-activated protein kinase in cerebellar granule neurons by polybrominated diphenyl ethers and polychlorinated biphenyls. Toxicol Appl Pharmacol 245 1 8 20171977
  23. Friedman DB Hill S Keller JW Merchant NB Levy SE Coffey RJ 2004 Proteome analysis of human colon cancer by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 4 793 811 14997500
  24. Gee JR Moser VC 2008 Acute postnatal exposure to brominated diphenylether 47 delays neuromotor ontogeny and alters motor activity in mice. Neurotoxicol Teratol 30 79 87 18166377
  25. Grabham PW Seale GE Bennecib M Goldberg DJ Vallee RB 2007 Cytoplasmic dynein and LIS1 are required for microtubule advance during growth cone remodeling and fast axonal outgrowth. J Neurosci 27 5823 5834 17522326 PMC6672755
  26. Hall CN Klein-Flugge MC Howarth C Attwell D 2012 Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J Neurosci 32 8940 8951 22745494 PMC3390246
  27. Hall PA Jung K Hillan KJ Russell SE 2005 Expression profiling the human septin gene family. J Pathol 206 269 278 15915442
  28. Hanari N Kannan K Miyake Y Okazawa T Kodavanti PR Aldous KM 2006 Occurrence of polybrominated biphenyls, polybrominated dibenzo-p-dioxins, and polybrominated dibenzofurans as impurities in commercial polybrominated diphenyl ether mixtures. Environ Sci Technol 40 4400 4405 16903277
  29. Herbstman JB Sjödin A Kurzon M Lederman SA Jones RS Rauh V 2010 Prenatal exposure to PBDEs and neurodevelopment. Environ Health Perspect 118 712 719; 10.1289/ehp.0901340 20056561 PMC2866690 · DOI
  30. Hofmann HD Kirsch M 2012 JAK2-STAT3 signaling: a novel function and a novel mechanism. JAKSTAT 1 191 193 24058769 PMC3670243
  31. Ibhazehiebo K Iwasaki T Kimura-Kuroda J Miyazaki W Shimokawa N Koibuchi N 2011 Disruption of thyroid hormone receptor-mediated transcription and thyroid hormone-induced Purkinje cell dendrite arborization by polybrominated diphenyl ethers. Environ Health Perspect 119 168 175; 10.1289/ehp.1002065 20870570 PMC3040602 · DOI
  32. Kater SB Mills LR 1991 Regulation of growth cone behavior by calcium. J Neurosci 11 891 899 2010811 PMC6575390
  33. Kodavanti PR 2005 Neurotoxicity of persistent organic pollutants: possible mode(s) of action and further considerations. Dose Response 3 273 305 18648619 PMC2475949
  34. Kodavanti PR Coburn CG Moser VC MacPhail RC Fenton SE Stoker TE 2010 Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects. Toxicol Sci 116 297 312 20375078
  35. Kodavanti PR Derr-Yellin EC Mundy WR Shafer TJ Herr DW Barone S 1998 Repeated exposure of adult rats to Aroclor 1254 causes brain region-specific changes in intracellular Ca2+ buffering and protein kinase C activity in the absence of changes in tyrosine hydroxylase. Toxicol Appl Pharmacol 153 186 198 9878590
  36. Kodavanti PRS Osorio C Royland JE Ramabhadran R Alzate O 2011 Aroclor-1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus. Toxicol Appl Pharmacol 256 290 299 21791222
  37. Kodavanti PRS, Senthilkumar K, Loganathan BG. 2008 Organohalogen pollutants and human health In International Encyclopedia of Public Health, Vol. 4 (Heggenhougen K, Quah S, eds). San Diego:Academic Press, 686–693
  38. Kodavanti PR Ward TR Ludewig G Robertson LW Birnbaum LS 2005 Polybrominated diphenyl ether (PBDE) effects in rat neuronal cultures: 14C-PBDE accumulation, biological effects, and structure-activity relationships. Toxicol Sci 88 181 192 16107548
  39. La Guardia MJ Hale RC Harvey E 2006 Detailed polybrominated diphenyl ether (PBDE) congener composition of the widely used penta-, octa-, and deca-PBDE technical flame-retardant mixtures. Environ Sci Technol 40 6247 6254 17120549
  40. Lein PJ Yang D Bachstetter AD Tilson HA Harry GJ Mervis RF 2007 Ontogenetic alterations in molecular and structural correlates of dendritic growth after developmental exposure to polychlorinated biphenyls. Environ Health Perspect 115 556 563; 10.1289/ehp.9773 17450224 PMC1852648 · DOI
  41. Lim L Hall C Leung T Mahadevan L Whatley S 1983 Neurone-specific enolase and creatine phosphokinase are protein components of rat brain synaptic plasma membranes. J Neurochem 41 1177 1182 6619855
  42. Lundin VF Leroux MR Stirling PC 2010 Quality control of cytoskeletal proteins and human disease. Trends Biochem Sci 35 288 297 20116259
  43. Mahadevan LC Whatley SA Leung TK Lim L 1984 The brain isoform of a key ATP-regulating enzyme, creatine kinase, is a phosphoprotein. Biochem J 222 139 144 6477506 PMC1144154
  44. Martínez-Solano L Reales-Calderón JA Nombela C Molero G Gil C 2009 Proteomics of RAW 264.7 macrophages upon interaction with heat-inactivated Candida albicans cells unravel an anti-inflammatory response. Proteomics 9 2995 3010 19526544
  45. Mazdai A Dodder NG Abernathy MP Hites RA Bigsby RM 2003 Polybrominated diphenyl ethers in maternal and fetal blood samples. Environ Health Perspect 111 1249 1252 12842781 PMC1241582
  46. McDonald TA 2005 Polybrominated diphenylether levels among United States residents: daily intake and risk of harm to the developing brain and reproductive organs. Integr Environ Assess Manag 1 343 354 16639901
  47. Mukherjee J Po BH Chiu JM Wu RS Qian PY Thiyagarajan V 2013 Polybrominated diphenyl ethers do not affect metamorphosis but alter the proteome of the invasive slipper limpet Crepidula onyx. Mar Pollut Bull 73 273 281 23743271
  48. Murphey RK Caruccio PC Getzinger M Westgate PJ Phillis RW 1999 Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: a role for retrograde motors. Dev Biol 209 86 97 10208745
  49. Murphy A Sunohara JR Sundaram M Ridgway ND McMaster CR Cook HW 2003 Induction of protein kinase C substrates, myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP), by amyloid beta-protein in mouse BV-2 microglial cells. Neurosci Lett 347 9 12 12865129
  50. Napoli E Hung C Wong S Guilivi C 2013 Toxicity of the flame-retardant BDE-49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN-deficient background. Toxicol Sci 132 196 210 23288049 PMC3693513
  51. O’Callaghan JP Sriram K 2005 Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf 4 433 442 15934851
  52. Pereira LC Miranda LF de Souza AO Dorta DJ 2014 BDE-154 induces mitochondrial permeability transition and impairs mitochondrial bioenergetics. J Toxicol Environ Health A 77 24 36 24555644
  53. Quintyne NJ Gill SR Eckley DM Crego CL Compton DA Schroer TA 1999 Dynactin is required for microtubule anchoring at centrosomes. J Cell Biol 147 321 334 10525538 PMC2174233
  54. Rice DC Reeve EA Herlihy A Zoeller RT Thompson WD Markowski VP 2007 Developmental delays and locomotor activity in the C57BL6/J mouse following neonatal exposure to the fully-brominated PBDE, decabromodiphenyl ether. Neurotoxicol Teratol 29 511 520 17482428
  55. Schecter A Päpke O Tung KC Joseph J Harris TR Dahlgren J 2005 Polybrominated diphenyl ether flame retardants in the U.S. population: current levels, temporal trends, and comparison with dioxins, dibenzofurans, and polychlorinated biphenyls. J Occup Environ Med 47 199 211 15761315
  56. Song J Li ZH He YT Liu CX Sun B Zhang CF 2014 Decabrominated diphenyl ether (BDE-209) and/or BDE-47 exposure alters protein expression in purified neural stem/progenitor cells determined by proteomics analysis. Int J Dev Neurosci 33 8 14 24239914
  57. Suzuki Y Nakagomi S Namikawa K Kiryu-Seo S Inagaki N Kaibuchi K 2003 Collapsin response mediator protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat. J Neurochem 86 1042 1050 12887701
  58. Viberg H Eriksson P 2011 Differences in neonatal neurotoxicity of brominated flame retardants, PBDE 99 and TBBPA, in mice. Toxicology 289 59 65 21820030
  59. Viberg H Fredriksson A Eriksson P 2003a Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Toxicol Appl Pharmacol 192 95 106 14550744
  60. Viberg H Fredriksson A Eriksson P 2004 Neonatal exposure to the brominated flame-retardant, 2,2´,4,4´,5-pentabromodiphenyl ether, decreases cholinergic nicotinic receptors in hippocampus and affects spontaneous behaviour in the adult mouse. Envirol Toxicol Pharmacol 17 61 65 21782714
  61. Viberg H Fredriksson A Jakobsson E Orn U Eriksson P 2003b Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development. Toxicol Sci 76 112 120 12915714
  62. Wilhelmus MM Verhaar R Andringa G Bol JG Cras P Shan L 2011 Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson’s disease brain. Brain Pathol 21 130 139 20731657 PMC8094245
  63. Winnik WM Dekroon RM Jeong JS Mocanu M Robinette JB Osorio C 2012 Analysis of proteins using DIGE and MALDI mass spectrometry. Methods Mol Biol 854 47 66 22311753
  64. Wold F. 1971 Enolase In The Enzymes, Vol. 5 (Boyer PD, ed). 3rd ed. New York:Academic Press, 499–538
  65. Zhang X Lei K Yuan X Wu X Zhuang Y Xu T 2009 SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron 64 173 187 19874786 PMC2788510

Cited by

Sorted by citations

Authors
Kodavanti, P. R. S., Royland, J. E., Osorio, C., Winnik, W. M., Ortiz, P., Lei, L., Ramabhadran, R., & Alzate, O.
Affiliations
  • Neurotoxicology Branch, and
  • Environmental Protection Agency (US)
  • University of North Carolina at Chapel Hill (US)
  • Systems Proteomics Center, and
Corresponding author
Kodavanti, Prasada Rao S.
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2014-12-19
Volume
123
Issue
5
Pages
428-436
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.1408504
PMC
PMC4421769
OpenAlex
W2324823308
Cited by
45
References
0
Citations by year
2025: 4 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 3
FWCI
3.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
U.S. Environmental Protection Agency
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords
polybrominated diphenyl ethers, DE-71, developmental neurotoxicity, perinatal exposure, cerebellum, hippocampus, protein expression profiling, mitochondrial bioenergetics, oxidative stress, apoptosis, calcium signaling, neuroplasticity, brominated flame retardants
MeSH terms
Animals, Animals, Newborn, Cerebellum, Female, Hippocampus, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Long-Evans, Rats, Tandem Mass Spectrometry, Halogenated Diphenyl Ethers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review