Abstract
Perfluorooctanesulfonate (PFOS) is an environmental contaminant found in human and animal tissues worldwide. The developing nervous system is thought to be particularly sensitive to PFOS by the fact that PFOS can cross blood–brain and placental barriers. Effect of gestational and lactational exposure to PFOS on central nervous system (CNS) in Wistar rats was investigated by the cross-foster model built with PFOS at 0 or 3.2 mg/kg food. Real-time reverse transcription-polymerase chain reaction was employed to evaluate the gene expression of calcium-dependent signaling molecules in rats’ hippocampus which are critical to the function of CNS. The expression of calcium-related signaling molecules, such as N-methyl-d-aspartate receptor subtype-2B (NR2B), calmodulin (CaM), Ca2+/calmodulin-dependent kinase II α (CaMKIIα) and cAMP-response element-binding (CREB) were increased in the PFOS exposure group at postnatal day 1 (PND 1). The decreased NR2B in the prenatal PFOS exposure group, the decreased CaM in the pre-/postnatal PFOS exposure group, the increased CaMKIIα in the whole-life PFOS exposure group and the increased CREB in the prenatal/whole-life PFOS exposure group was observed at PND 7. At PND 35, rats exhibited the decreased NR2B in the pre-/postnatal and the whole-life PFOS exposure group, and the decreased CaM in the postnatal PFOS group. The results indicate that perinatal exposure to PFOS during the critical period of development of the brain may have neurotoxic effect on CNS by mediating the molecules of calcium signaling pathway.
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Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SMJ (2003) Neuroendocrine effects of perfluorooctane sulfonate in rats. Environ Health Perspect 111:1485–1489. doi:10.1289/ehp
Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13–26. doi:10.1016/S0896-6273(00)80510-3
Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39. doi:10.1038/361031a0
Butenhoff JL, Olsen GW, Pfahles HA (2006) The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum. Environ Health Perspect 114:1776–1782. doi:10.1289/ehp.9060
Butenhoff JL, Ehresman DJ, Chang SC, Parker GA, Stump DG (2009) Gestational and lactational exposure to potassium perfluorooctanesulfonate (K + PFOS) in rats: developmental neurotoxicity. Reprod Toxicol 27:319–330. doi:10.1016/j.reprotox.2008.12.010
Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL (2007) Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect 115:1596–1602. doi:10.1289/ehp.10598
Chang SC, Ehresman DJ, Bjork JA, Wallace KB, Parker GA, Stump DG, Butenhoff JL (2009) Gestational and lactational exposure to potassium perfluorooctanesulfonate (K + PFOS) in rats: toxicokinetics, thyroid hormone status, and related gene expression. Reprod Toxicol 3–4:387–399. doi:10.1016/j.reprotox.2009.01.005
Christopher L (2009) Perfluoroalkyl acids: recent activities and research progress. Reprod Toxicol 27:209–211. doi:10.1016/j.reprotox.2009.02.011
Fuentes S, Colomina MT, Vicens P, Domingo JL (2007a) Influence of maternal restraint stress on the long-lasting effects induced by prenatal exposure to perfluorooctane sulfonate (PFOS) in mice. Toxicol Lett 171:162–170. doi:10.1016/j.toxlet.2007.05.006
Fuentes S, Colomina MT, Vicens P, Franco PN, Domingo JL (2007b) Concurrent exposure to perfluorooctane sulfonate (PFOS) and restraint stress during pregnancy in mice: effects on postnatal development and behavior of the offspring. Toxicol Sci 98:589–598. doi:10.1093/toxsci/kfm121
Fuentes S, Vicens P, Colomina MT, Domingo JL (2007c) Behavioral effects in adult mice exposed to perfluorooctane sulfonate (PFOS). Toxicology 242:123–129. doi:10.1016/j.tox.2007.09.012
Grasty RC, Bjork JA, Wallace KB, Wolf DC, Lau CS, Rogers JM (2005) Effects of prenatal perfluorooctane sulfonate (PFOS) exposure on lung maturation in the perinatal rat. Birth Defects Res B Dev Reprod Toxicol 74:405–416. doi:10.1002/bdrb.20059
Hahn K, DeBiasio R, Taylor DL (1992) Patterns of elevated free calcium and calmodulin activation in living cells. Nature 359:736–738. doi:10.1038/359736a0
Hansen KJ, Clemen LA, Ellefson ME, Johnson HO (2001) Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sci Technol 35:766–770. doi:10.1021/es001489z
Harada KJ, Xu F, Ono K, Iijima T, Koizumi A (2005) Effects of PFOS and PFOA on L-type Ca2+ currents in guinea-pig ventricular myocytes. Biochem Biophys Res Commun 329:487–494. doi:10.1016/j.bbrc.2005.01.163
Harada KH, Ishii TM, Takatsuka K, Koizumi A, Ohmori H (2006) Effects of perfluorooctane sulfonate on action potentials and currents in cultured rat cerebellar Purkinje cells. Biochem Biophys Res Commun 351:240–245. doi:10.1016/j.bbrc.2006.10.038
Harada KH, Hashida S, Kaneko T, Takenaka K, Minata M, Inoue K, Saito N, Koizumi A (2007) Biliary excretion and cerebrospinal fluid partition of perfluorooctanoate and perfluorooctane sulfonate in humans. Environ Toxicol Pharmacol 24:134–139. doi:10.1016/j.etap.2007.04.003
Hardingham GE, Bading H (2003) The Yin and Yang of NMDA receptor signaling. Trends Neurosci 26:81–89. doi:10.1016/S0166-2236(02)00040-1
Houde M, Martin JW, Letcher RJ, Solomon KR, Muir DC (2006) Biological monitoring of polyfluoroalkyl substances: a review. Environ Sci Technol 40:3463–3473. doi:10.1021/es052580b
Inoue K, Okada F, Ito R, Kato S, Sasaki S, Nakajima S et al (2004) Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy. Environ Health Perspect 112:1204–1207. doi:10.1289/ehp.6864
Johansson N, Fredriksson A, Eriksson P (2008) Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology 29:160–169. doi:10.1016/j.neuro.2007.10.008
Johansson N, Eriksson P, Viberg H (2009) Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. Toxicol Sci 108:412–418. doi:10.1093/toxsci/kfp029
Johnson JD, Gibson SJ, Ober RE (1984) Cholestyramine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium [14C]perfluorooctanoate or potassium [14C]perfluorooctanesulfonate. Fundam Appl Toxicol 4:972–976
Jones PD, Hu W, De Coen W, Newsted JL, Giesy JP (2003) Binding of perfluorinated fatty acids to serum proteins. Environ Toxicol Chem 22:2639–2649. doi:10.1897/02-553
Kärrman A, Ericson I, van Bavel B, Darnerud PO, Aune M, Glynn A et al (2007) Exposure of perfluorinated chemicals through lactation: levels of matched human milk and serum and a temporal trend, 1996–2004, in Sweden. Environ Health Perspect 115:226–230. doi:10.1289/ehp.9491
Lau C, Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Stanton ME et al (2003) Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II. Postnatal evaluation. Toxicol Sci 74:382–392. doi:10.1093/toxsci/kfg122
Lau C, Butenhoff JL, Rogers JM (2004) The developmental toxicity of perfluoroalkyl acids and their derivatives. Toxicol Appl Pharmacol 198:231–241. doi:10.1016/j.taap.2003.11.031
Lau C, Thibodeaux JR, Das K, Ehresman DJ, Tanaka S, Froehlich J, Butenhoff JL (2006) Evaluation of perfluorooctane sulfonate in the rat brain. Toxicologist 90, S118 (Abstract ID: 576)
Lau C, Anitole K, Hodes C, Lai D, Pfahles HA, Seed J (2007) Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 99:366–394. doi:10.1093/toxsci/kfm128
Liao CY, Li XY, Wu B, Duan S, Jiang GB (2008) Acute enhancement of synaptic transmission and chronic inhibition of synaptogenesis induced by perfluorooctane sulfonate through mediation of voltage-dependent calcium channel. Environ Sci Technol 42:5335–5341. doi:10.1021/es800018k
Liao CY, Cui L, Zhou QF, Duan SM, Jiang GB (2009) Effects of perfluorooctane sulfonate on ion channels and glutamate-activated current in cultured rat hippocampal neurons. Environ Toxicol Pharmacol 27:338–344. doi:10.1016/j.etap.2008.11.013
Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623. doi:10.1016/S0896-6273(02)00828-0
Lonze BE, Riccio A, Cohen S, Ginty DD (2002) Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34:371–385. doi:10.1016/S0896-6273(02)00686-4
Luebker DJ, Case MT, York RG, Moore JA, Hansen KJ, Butenhoff JL (2005) Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats. Toxicology 215:126–148. doi:10.1016/j.tox.2005.07.018
Maestri L, Negri S, Ferrari M, Ghittori S, Fabris F, Danesino P, Imbriani M (2006) Determination of perfluorooctanoic acid and perfluorooctanesulfonate in human tissues by liquid chromatography/single quadrupole mass spectrometry. Rapid Commun Mass Spectrom 20:2728–2734. doi:10.1016/j.jchromb.2004.07.014
Mantamadiotis T, Lemberger T, Bleckmann SC, Kern H et al (2002) Disruption of CREB function in brain leads to neurodegeneratio. Nat Genet 31:47–54. doi:10.1038/ng882
Matsubara E, Harada K, Inoue K, Koizumi A (2006) Effects of perfluorinated amphiphiles on backward swimming in Paramecium caudatum. Biochem Biophys Res Commun 339:554–561. doi:10.1016/j.bbrc.2005.11.048
Midasch O, Drexler H, Hart N, Beckmann MW, Angerer J (2007) Transplacental exposure of neonates to perfluorooctanesulfonate and perfluorooctanoate: a pilot study. Int Arch Occup Environ Health 80:643–648. doi:10.1007/s00420-006-0165-9
Monroy R, Morrison K, Teo K, Atkinson S, Kubwabo C, Stewart B et al (2008) Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples. Environ Res 108:56–62. doi:10.1016/j.envres.2008.06.001
Sala C, Rudolph-Correia S, Sheng M (2000) Developmentally regulated NMDA receptor-dependent dephosphorylation of cAMP response element-binding protein (CREB) in hippocampal neurons. J Neurosci 20:3529–3536
Saucerman JJ, Bers DM (2008) Calmodulin mediates differential sensitivity of CaMKII and calcineurin to Local Ca2+ in cardiac myocytes. Biophys J 95:4597–4612. doi:10.1529/biophysj.108.128728
Schäfer S, Bickmeyer U, Koehler A (2009) Measuring Ca2+ -signalling at fertilization in the sea urchin Psammechinus miliaris: alterations of this Ca2+-signal by copper and 2, 4, 6-tribromophenol. Comp Biochem Physiol C Toxicol Phamacol 150(2):261–269. doi:10.1016/j.cbpc.2009.05.004
Slotkin TA, MacKillop EA, Melnick RL, Thayer KA, Seidler FJ (2008) Developmental neurotoxicity of perfluorinated chemicals modeled in vitro. Environ Health Perspect 116:716–722. doi:10.1289/ehp.11253
So MK, Yamashita N, Taniyasu S, Jiang Q, Giesy JP, Chen K et al (2006) Health risks in infants associated with exposure to perfluorinated compounds in human breast milk from Zhoushan, China. Environ Sci Technol 40:2924–2929. doi:10.1021/es060031f
Spliethoff HM, Tao L, Shaver SM, Aldous KM, Pass KA, Kannan K et al (2008) Use of newborn screening program blood spots for exposure assessment: declining levels of perfluorinated compounds in New York state infants. Environ Sci Technol 42:5361–5367. doi:10.1021/es8006244
Stead JD, Neal C, Meng F, Wang YJ, Evans S, Vazquez DM, Watson SJ, Akil H (2006) Transcriptional profiling of the developing rat brain reveals that the most dramatic regional differentiation in gene expression occurs postpartum. J Neurosci 26:345–353. doi:10.1523/JNEUROSCI.2755-05.2006
Tao L, Kannan K, Wong CM, Arcaro KF, Butenhoff JL (2008) Perfluorinated compounds in human milk from Massachusetts. U.S.A. Environ Sci Technol 42:3096–3101. doi:10.1021/es702789k
Vanhoutte P, Bading H (2003) Opposing roles of synaptic and extrasynaptic NMDA receptors in neuronal calcium signalling and BDNF gene regulation. Curr Opin Neurobiol 13:366–371. doi:10.1016/S0959-4388(03)00073-4
Volkel W, Genzel BO, Demmelmair H, Gebauer C, Koletzko B, Twardella D et al (2008) Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) in human breast milk: results of a pilot study. Int J Hyg Environ Health 211:440–446. doi:10.1016/j.ijheh.2007.07.024
Wollmuth LP, Sobolevsky AI (2004) Structure and gating of the glutamate receptor ion channel. Trends Neurosci 27:321–328. doi:10.1016/j.tins.2004.04.005
Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765–1769. doi:10.1126/science.288.5472.1765
Xia ZG, Storm DR (2005) The role of calmodulin as a signal integrator for synaptic plasticity. Nat Rev Neurosci 6:267–276. doi:10.1038/nrn1647
Yamakura T, Shimoji K (1999) Subunit- and site-specific pharmacology of the NMDA receptor channel. Prog Neurobiol 59:279–298. doi:10.1016/S0301-0082(99)00007-6
Zacharias DA, DeMarcoa SJ, Strehler EE (1997) mRNA expression of the four isoforms of the human plasma membrane Ca2+-ATPase in the human hippocampus. Mol Brain Res 45:173–176. doi:10.1016/S0169-328X(97)00009-0
Zhang SY, Liu Q, Liu QJ, Duan HW, He FS, Zheng YX (2006) Effect of 2, 5-hexanedione on calcium homeostasis of motor neuron. Chin J Ind Hyg Occup Dis 24:270–272
Zuo ZH, Cai Jl, Wang XL, Li BW, Wang CG, Chen YX (2009) Acute administration of tributyltin and trimethyltin modulate glutamate and N-methyl-d-aspartate receptor signaling pathway in Sebastiscus marmoratus. Aquatic Toxicol 92:44–49. doi:10.1016/j.aquatox.2009.01.008
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We thank National Nature Science Foundation of China (No.20837004 and No.30771772) for financial support.
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Liu, X., Liu, W., Jin, Y. et al. Effect of gestational and lactational exposure to perfluorooctanesulfonate on calcium-dependent signaling molecules gene expression in rats’ hippocampus. Arch Toxicol 84, 71–79 (2010). https://doi.org/10.1007/s00204-009-0467-2
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DOI: https://doi.org/10.1007/s00204-009-0467-2