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Lanthanum Chloride Impairs Learning and Memory and Induces Dendritic Spine Abnormality by Down-Regulating Rac1/PAK Signaling Pathway in Hippocampus of Offspring Rats

  • Wenchang Sun
  • Jinghua YangEmail author
  • Yunting Hong
  • Hui Yuan
  • Jianbo Wang
  • Yanqiang Zhang
  • Xiaobo Lu
  • Cuihong Jin
  • Shengwen Wu
  • Yuan CaiEmail author
Original Research
  • 40 Downloads

Abstract

Lanthanum (La) is a natural rare earth element. It has neurotoxic effects which can impair learning and memory in humans. However, its mechanism of neurotoxicity is unclear. Learning and memory are coordinated by dendritic spines which form tiny protruding structures on the dendritic branches of neurons. This study investigated the effect of LaCl3 exposure to pregnant and lactating rats on the offspring rats’ learning and memory ability. In this study, rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, 0.5% LaCl3, respectively, and this was done from conception to the end of the location. The effects of LaCl3 on spatial learning and memory ability in offspring rats and in the development of dendritic spines in CA1 pyramidal cells were investigated. The results showed that LaCl3 impaired spatial learning and memory ability in offspring rats, and decreased dendritic spine density during development. In addition, LaCl3 can affect the expression of CaMKII, miRNA132, p250GAP, Tiam1, PARD3, and down-regulated the activation of Rac1 which led to a decrease in the expression of Rac1/PAK signaling pathway and downstream regulatory proteins Cortactin and actin-related protein 2/3 complex (Arp2/3 complex). This study indicated that the learning and memory impairment and the decrease of dendritic spine density in the offspring of LaCl3 exposure may be related to the down-regulation of the Rac1/PAK signaling pathway regulated by Tiam1 and p250GAP.

Keywords

Lanthanum Hippocampus Learning and memory Rac1 Dendritic spine 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 81773469, 81373024, and 81673220).

Supplementary material

10571_2019_748_MOESM1_ESM.docx (18 kb)
Electronic supplementary material 1 (DOCX 18 kb)

References

  1. Allison JE, Boutin C, Carpenter D, Ellis DM, Parsons JL (2015) Cerium chloride heptahydrate (CeCl3. 7H2O) induces muscle paralysis in the generalist herbivore, Melanoplus sanguinipes (Fabricius) (Orthoptera: Acrididae), fed contaminated plant tissues. Chemosphere 120:674–679.  https://doi.org/10.1016/j.chemosphere.2014.09.058 CrossRefPubMedGoogle Scholar
  2. Beltran-Campos V, Prado-Alcala RA, Leon-Jacinto U, Aguilar-Vazquez A, Quirarte GL, Ramirez-Amaya V, Diaz-Cintra S (2011) Increase of mushroom spine density in CA1 apical dendrites produced by water maze training is prevented by ovariectomy. Brain Res 1369:119–130.  https://doi.org/10.1016/j.brainres.2010.10.105 CrossRefPubMedGoogle Scholar
  3. Berry KP, Nedivi E (2017) Spine dynamics: are they all the same? Neuron 96:43–55.  https://doi.org/10.1016/j.neuron.2017.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bian WJ, Miao WY, He SJ, Qiu Z, Yu X (2015) Coordinated spine pruning and maturation mediated by inter-spine competition for cadherin/catenin complexes. Cell 162:808–822.  https://doi.org/10.1016/j.cell.2015.07.018 CrossRefPubMedGoogle Scholar
  5. Burrell BD, Li Q (2008) Co-induction of long-term potentiation and long-term depression at a central synapse in the leech. Neurobiol Learn Mem 90:275–279.  https://doi.org/10.1016/j.nlm.2007.11.004 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chagnon MJ, Wu CL, Nakazawa T, Yamamoto T, Noda M, Blanchetot C, Tremblay ML (2010) Receptor tyrosine phosphatase sigma (RPTPsigma) regulates, p250GAP, a novel substrate that attenuates Rac signaling. Cell Signal 22:1626–1633.  https://doi.org/10.1016/j.cellsig.2010.06.001 CrossRefPubMedGoogle Scholar
  7. Chen Z-y, Zhu X-d (2008) Accumulation of rare earth elements in bone and its toxicity and potential hazard to health. J Ecol Rural Environ 24:88–91Google Scholar
  8. Chen LY, Rex CS, Babayan AH, Kramar EA, Lynch G, Gall CM, Lauterborn JC (2010) Physiological activation of synaptic Rac > PAK (p-21 activated kinase) signaling is defective in a mouse model of fragile X syndrome. J Neurosci 30:10977–10984.  https://doi.org/10.1523/jneurosci.1077-10.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chen F et al (2015) Terbium-doped gadolinium oxide nanoparticles prepared by laser ablation in liquid for use as a fluorescence and magnetic resonance imaging dual-modal contrast agent. Phys Chem Chem Phys 17:1189–1196.  https://doi.org/10.1039/c4cp04380d CrossRefPubMedGoogle Scholar
  10. Consani S, Balic-Zunic T, Cardinale AM, Sgroi W, Giuli G (2018) A novel synthesis routine for woodwardite and its affinity towards light (La, Ce, Nd) and heavy (Gd and Y). Rare Earth Elem 11:150.  https://doi.org/10.3390/ma11010130 CrossRefGoogle Scholar
  11. d’Aquino L et al (2009) Effect of some rare earth elements on the growth and lanthanide accumulation in different Trichoderma strains. Soil Biol Biochem 41:2406–2413.  https://doi.org/10.1016/j.soilbio.2009.08.012 CrossRefGoogle Scholar
  12. D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36:60–90CrossRefGoogle Scholar
  13. Duman JG, Tzeng CP, Tu YK, Munjal T, Schwechter B, Ho TS, Tolias KF (2013) The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites. J Neurosci 33:6964–6978.  https://doi.org/10.1523/jneurosci.3978-12.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Dumitriu D, Hao J, Hara Y et al (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30(22):7507–7515.  https://doi.org/10.1523/jneurosci.6410-09.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Eisenhour D, Reisch F (2006) Industrial minerals and rocks: commodities, markets, and uses. Society for Mining, Metallurgy, and Exploration, ColoradoGoogle Scholar
  16. Fan G, Yuan Z, Zheng H, Liu Z (2004) Study on the effects of exposure to rare earth elements and health-responses in children aged 7-10 years. J Hygiene Res 33:23–28Google Scholar
  17. Feng L et al (2006) Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett 165:112–120.  https://doi.org/10.1016/j.toxlet.2006.02.003 CrossRefPubMedGoogle Scholar
  18. Gao X, Yang J, Li Y et al (2019) Lanthanum chloride induces autophagy in rat hippocampus through ROS-mediated JNK and AKT/mTOR signaling pathways. Metallomics 11(2):439–453.  https://doi.org/10.1039/c8mt00295a CrossRefPubMedGoogle Scholar
  19. Greenhill SD, Juczewski K, de Haan AM, Seaton G, Fox K, Hardingham NR (2015) NEURODEVELOPMENT. Adult cortical plasticity depends on an early postnatal critical period. Science (New York, NY) 349:424–427.  https://doi.org/10.1126/science.aaa8481 CrossRefGoogle Scholar
  20. Grossman AW, Aldridge GM, Weiler IJ, Greenough WT (2006) Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond. J Neurosci 26:7151–7155.  https://doi.org/10.1523/jneurosci.1790-06.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gwenzi W, Mangori L, Danha C, Chaukura N, Dunjana N, Sanganyado E (2018) Sources, behaviour, and environmental and human health risks of high-technology rare earth elements as emerging contaminants. Sci Total Environ 636:299–313.  https://doi.org/10.1016/j.scitotenv.2018.04.235 CrossRefPubMedGoogle Scholar
  22. Haditsch U et al (2009) A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory. Mol Cell Neurosci 41:409–419.  https://doi.org/10.1016/j.mcn.2009.04.005 CrossRefPubMedPubMedCentralGoogle Scholar
  23. He X, Zhang Z, Zhang H, Zhao Y, Chai Z (2008) Neurotoxicological evaluation of long-term lanthanum chloride exposure in rats. Toxicol Sci 103:354–361.  https://doi.org/10.1093/toxsci/kfn046 CrossRefPubMedGoogle Scholar
  24. Hedrick NG, Harward SC, Hall CE, Murakoshi H, McNamara JO, Yasuda R (2016) Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature 538:104–108.  https://doi.org/10.1038/nature19784 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Hu X et al (2018) Lanthanum chloride impairs memory in rats by disturbing the glutamate-glutamine cycle and over-activating NMDA receptors. Food Chem Toxicol 113:1–13.  https://doi.org/10.1016/j.fct.2018.01.023 CrossRefPubMedGoogle Scholar
  26. Impey S et al (2010) An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling. Mol Cell Neurosci 43:146–156.  https://doi.org/10.1016/j.mcn.2009.10.005 CrossRefPubMedGoogle Scholar
  27. Jiang M et al (2013) Dendritic arborization and spine dynamics are abnormal in the mouse model of MECP2 duplication syndrome. J Neurosci 33:19518–19533.  https://doi.org/10.1523/jneurosci.1745-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Joensuu M, Lanoue V, Hotulainen P (2018) Dendritic spine actin cytoskeleton in autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 84:362–381.  https://doi.org/10.1016/j.pnpbp.2017.08.023 CrossRefPubMedGoogle Scholar
  29. Kim IH et al (2013) Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. J Neurosci 33:6081–6092.  https://doi.org/10.1523/jneurosci.0035-13.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kim IH et al (2015) Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. Nat Neurosci 18:883–891.  https://doi.org/10.1038/nn.4015 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Li JG, Chu J, Pratico D (2018) Downregulation of autophagy by 12/15Lipoxygenase worsens the phenotype of an Alzheimer’s disease mouse model with plaques, tangles, and memory impairments. Mol Psychiatry.  https://doi.org/10.1038/s41380-018-0268-1 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Liu H, Yang J, Liu Q et al (2014) Lanthanum chloride impairs spatial memory through ERK/MSK1 signaling pathway of hippocampus in rats. Neurochem Res 39(12):2479–2491.  https://doi.org/10.1007/s11064-014-1452-6 CrossRefPubMedGoogle Scholar
  33. Luscher C, Nicoll RA, Malenka RC, Muller D (2000) Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci 3:545–550.  https://doi.org/10.1038/75714 CrossRefPubMedGoogle Scholar
  34. Mertens AE, Pegtel DM, Collard JG (2006) Tiam1 takes PARt in cell polarity. Trends Cell Biol 16:308–316.  https://doi.org/10.1016/j.tcb.2006.04.001 CrossRefPubMedGoogle Scholar
  35. Mi Z, Si T, Kapadia K, Li Q, Muma NA (2017) Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines. Neuropharmacology 117:93–105.  https://doi.org/10.1016/j.neuropharm.2017.01.034 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Miao L, Ma Y, Xu R, Yan W (2011) Environmental biogeochemical characteristics of rare earth elements in soil and soil-grown plants of the Hetai goldfield, Guangdong Province, China. Environ Earth Sci 63:501–511.  https://doi.org/10.1007/s12665-010-0718-9 CrossRefGoogle Scholar
  37. Mleczek P, Borowiak K, Budka A, Niedzielski P (2018) Relationship between concentration of rare earth elements in soil and their distribution in plants growing near a frequented road. Environ Sci Pollut Res Int.  https://doi.org/10.1007/s11356-018-2428-x CrossRefPubMedPubMedCentralGoogle Scholar
  38. Nakazawa T, Kuriu T, Tezuka T, Umemori H, Okabe S, Yamamoto T (2008) Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP. J Neurochem 105:1384–1393.  https://doi.org/10.1111/j.1471-4159.2008.05335.x CrossRefPubMedGoogle Scholar
  39. Nishijima H, Ueno T, Funamizu Y, Ueno S, Tomiyama M (2018) Levodopa treatment and dendritic spine pathology. Mov Disord 33:877–888.  https://doi.org/10.1002/mds.27172 CrossRefPubMedGoogle Scholar
  40. Okamoto K, Bosch M, Hayashi Y (2009) The roles of CaMKII and F-actin in the structural plasticity of dendritic spines: a potential molecular identity of a synaptic tag? Physiology (Bethesda, Md) 24:357–366.  https://doi.org/10.1152/physiol.00029.2009 CrossRefGoogle Scholar
  41. Olias M, Ceron JC, Fernandez I, De la Rosa J (2005) Distribution of rare earth elements in an alluvial aquifer affected by acid mine drainage: the Guadiamar aquifer (SW Spain). Environ Pollut 135:53–64.  https://doi.org/10.1016/j.envpol.2004.10.014 CrossRefPubMedGoogle Scholar
  42. Ota Y, Zanetti AT, Hallock RM (2013) The role of astrocytes in the regulation of synaptic plasticity and memory formation. Neural Plast 2013:185463.  https://doi.org/10.1155/2013/185463 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Penzes P, Rafalovich I (2012) Regulation of the actin cytoskeleton in dendritic spines. Adv Exp Med Biol 970:81–95.  https://doi.org/10.1007/978-3-7091-0932-8_4 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Penzes P, Cahill ME, Jones KA, Srivastava DP (2008) Convergent CaMK and RacGEF signals control dendritic structure and function. Trends Cell Biol 18:405–413.  https://doi.org/10.1016/j.tcb.2008.07.002 CrossRefPubMedGoogle Scholar
  45. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14:285–293.  https://doi.org/10.1038/nn.2741 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Pyronneau A, He Q, Hwang JY (2017) Aberrant Rac1-cofilin signaling mediates defects in dendritic spines, synaptic function, and sensory perception in fragile X syndrome. Sci Signal 10:eaan0852.  https://doi.org/10.1126/scisignal.aan0852 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Rainbow PS (2007) Trace metal bioaccumulation: models, metabolic availability and toxicity. Environ Int 33:576–582.  https://doi.org/10.1016/j.envint.2006.05.007 CrossRefPubMedGoogle Scholar
  48. Redies C, Hertel N, Hubner CA (2012) Cadherins and neuropsychiatric disorders. Brain Res 1470:130–144.  https://doi.org/10.1016/j.brainres.2012.06.020 CrossRefPubMedGoogle Scholar
  49. Sala C, Segal M (2014) Dendritic spines: the locus of structural and functional plasticity. Physiol Rev 94:141–188.  https://doi.org/10.1152/physrev.00012.2013 CrossRefPubMedGoogle Scholar
  50. Spence EF, Kanak DJ (2016) The Arp2/3 complex is essential for distinct stages of spine synapse maturation including synapse unsilencing. J Neurosci 36:9696–9709.  https://doi.org/10.1523/jneurosci.0876-16.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Spires TL et al (2005) Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 25:7278–7287.  https://doi.org/10.1523/jneurosci.1879-05.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Sun Y et al (2018) Lanthanum chloride reduces lactate production in primary culture rat cortical astrocytes and suppresses primary co-culture rat cortical astrocyte-neuron lactate transport. Arch Toxicol 92:1407–1419.  https://doi.org/10.1007/s00204-017-2148-x CrossRefPubMedGoogle Scholar
  53. Tolias KF, Bikoff JB, Kane CG, Tolias CS, Hu L, Greenberg ME (2007) The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development. Proc Natl Acad Sci USA 104:7265–7270.  https://doi.org/10.1073/pnas.0702044104 CrossRefPubMedGoogle Scholar
  54. Tsai J, Grutzendler J, Duff K, Gan WB (2004) Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nat Neurosci 7:1181–1183.  https://doi.org/10.1038/nn1335 CrossRefPubMedGoogle Scholar
  55. Uruno T et al (2001) Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nat Cell Biol 3:259–266.  https://doi.org/10.1038/35060051 CrossRefPubMedGoogle Scholar
  56. Wang L, Liang T, Kleinman PJ, Cao H (2011) An experimental study on using rare earth elements to trace phosphorous losses from nonpoint sources. Chemosphere 85:1075–1079.  https://doi.org/10.1016/j.chemosphere.2011.07.038 CrossRefPubMedGoogle Scholar
  57. Wang B, Wu Q, Lei L et al (2019) Long-term social isolation inhibits autophagy activation, induces postsynaptic dysfunctions and impairs spatial memory. Exp Neurol 311:213–224.  https://doi.org/10.1016/j.expneurol.2018.09.009 CrossRefPubMedGoogle Scholar
  58. Wayman GA et al (2008) An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci USA 105:9093–9098.  https://doi.org/10.1073/pnas.0803072105 CrossRefPubMedGoogle Scholar
  59. Weed SA, Karginov AV, Schafer DA, Weaver AM, Kinley AW, Cooper JA, Parsons JT (2000) Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex. J Cell Biol 151:29–40CrossRefGoogle Scholar
  60. Wegner AM, Nebhan CA, Hu L, Majumdar D, Meier KM, Weaver AM, Webb DJ (2008) N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J Biol Chem 283:15912–15920.  https://doi.org/10.1074/jbc.m801555200 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Wen B, Liu Y, Hu XY, Shan XQ (2006) Effect of earthworms (Eisenia fetida) on the fractionation and bioavailability of rare earth elements in nine Chinese soils. Chemosphere 63:1179–1186.  https://doi.org/10.1016/j.chemosphere.2005.09.002 CrossRefPubMedGoogle Scholar
  62. Wu J, Yang J, Liu Q, Wu S, Ma H, Cai Y (2013) Lanthanum induced primary neuronal apoptosis through mitochondrial dysfunction modulated by Ca(2)(+) and Bcl-2 family. Biol Trace Elem Res 152(1):125–134.  https://doi.org/10.1007/s12011-013-9601-3 CrossRefPubMedGoogle Scholar
  63. Xie Z et al (2007) Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron 56:640–656.  https://doi.org/10.1016/j.neuron.2007.10.005 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yang J et al (2009) Lanthanum chloride impairs memory, decreases pCaMK IV, pMAPK and pCREB expression of hippocampus in rats. Toxicol Lett 190:208–214.  https://doi.org/10.1016/j.toxlet.2009.07.016 CrossRefPubMedGoogle Scholar
  65. Yang J, Liu Q, Wu S, Xi Q, Cai Y (2013) Effects of lanthanum chloride on glutamate level, intracellular calcium concentration and caspases expression in the rat hippocampus. Biometals 26(1):43–59.  https://doi.org/10.1007/s10534-012-9593-z CrossRefPubMedGoogle Scholar
  66. Yasuda R (2017) Biophysics of biochemical signaling in dendritic spines: implications in synaptic plasticity. Biophys J 113:2152–2159.  https://doi.org/10.1016/j.bpj.2017.07.029 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Zagrebelsky M, Holz A, Dechant G, Barde YA, Bonhoeffer T, Korte M (2005) The p75 neurotrophin receptor negatively modulates dendrite complexity and spine density in hippocampal neurons. J Neurosci 25:9989–9999.  https://doi.org/10.1523/jneurosci.2492-05.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Zhang H, Webb DJ, Asmussen H, Niu S, Horwitz AF (2005) A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC. J Neurosci 25:3379–3388.  https://doi.org/10.1523/jneurosci.3553-04.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Zhang L et al (2017a) The effect of nuclear factor erythroid 2-related factor/antioxidant response element signalling pathway in the lanthanum chloride-induced impairment of learning and memory in rats. J Neurochem 140:463–475.  https://doi.org/10.1111/jnc.13895 CrossRefPubMedGoogle Scholar
  70. Zhang L et al (2017b) Activation of Nrf2/ARE signaling pathway attenuates lanthanum chloride induced injuries in primary rat astrocytes. Metallomics 9:1120–1131.  https://doi.org/10.1039/c7mt00182g CrossRefPubMedGoogle Scholar
  71. Zhao YG, Sun L, Miao G et al (2015) The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis. Autophagy 11(6):881–890.  https://doi.org/10.1080/15548627.2015.1047127 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Zhao ZH, Zheng G, Wang T et al (2018) Low-level gestational lead exposure alters dendritic spine plasticity in the hippocampus and reduces learning and memory in rats. Sci Rep 8(1):3533.  https://doi.org/10.1038/s41598-018-21521-8 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Zheng L et al (2013) Lanthanum chloride impairs spatial learning and memory and downregulates NF-kappa B signalling pathway in rats. Arch Toxicol 87:2105–2117.  https://doi.org/10.1007/s00204-013-1076-7 CrossRefPubMedGoogle Scholar
  74. Zhu W, Xu S, Shao P, Zhang H, Wu D, Yang W, Feng J (1997) Bioelectrical activity of the central nervous system among populations in a rare earth element area. Biol Trace Elem Res 57:71–77.  https://doi.org/10.1007/bf02803871 CrossRefPubMedGoogle Scholar
  75. Zoghbi HY, Bear MF (2012) Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a009886 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wenchang Sun
    • 1
  • Jinghua Yang
    • 1
    Email author
  • Yunting Hong
    • 1
  • Hui Yuan
    • 1
  • Jianbo Wang
    • 1
  • Yanqiang Zhang
    • 1
  • Xiaobo Lu
    • 1
  • Cuihong Jin
    • 1
  • Shengwen Wu
    • 1
  • Yuan Cai
    • 1
    Email author
  1. 1.Department of Toxicology, School of Public HealthChina Medical UniversityShenyangPeople’s Republic of China

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