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Effects of Developmental Exposure to TiO2 Nanoparticles on Synaptic Plasticity in Hippocampal Dentate Gyrus Area: an In Vivo Study in Anesthetized Rats

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Abstract

With the increasing applications of titanium dioxide nanoparticles (TiO2 NPs) in industry and daily life, an increasing number of studies showed that TiO2 NPs may have negative effects on the respiratory or metabolic circle systems of organisms, while very few studies focused on the brain central nervous system (CNS). Synaptic plasticity in hippocampus is believed to be associated with certain high functions of CNS, such as learning and memory. Thus, in this study, we investigated the effects of developmental exposure to TiO2 NPs on synaptic plasticity in rats’ hippocampal dentate gyrus (DG) area using in vivo electrophysiological recordings. The input/output (I/O) functions, paired-pulse reaction (PPR), field excitatory postsynaptic potential, and population spike amplitude were measured. The results showed that the I/O functions, PPR, and long-term potentiation were all attenuated in lactation TiO2 NPs-exposed offspring rats compared with those in the control group. However, in the pregnancy TiO2 NPs exposure group, only PPR was attenuated significantly. These findings suggest that developmental exposure to TiO2 NPs could affect synaptic plasticity in offspring’s hippocampal DG area in vivo, which indicates that developmental brains, especially in lactation, are susceptible to TiO2 NPs exposure. This study reveals the potential toxicity of TiO2 NPs in CNS. It may give some hints on the security of TiO2 NPs production and application and shed light on its future toxicological studies.

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References

  1. Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8

    Article  PubMed  Google Scholar 

  2. Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  PubMed  Google Scholar 

  3. Colvin VL (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21:1166–1170

    Article  PubMed  CAS  Google Scholar 

  4. Hoet PHM, Nemmar A, Nemery B (2004) Health impact of nanomaterials? Nat Biotechnol 22:19

    Article  PubMed  CAS  Google Scholar 

  5. Grassian VH, O’Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS (2007) Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environ Health Persp 115:397–402

    Article  CAS  Google Scholar 

  6. Wang JX, Zhou GQ, Chen CY, Yu HW, Wang TC, Ma YM, Jia G, Gao YX, Li B, Sun J, Li YF, Jiao F, Zhao YL, Chai ZF (2007) Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett 168:176–185

    Article  PubMed  CAS  Google Scholar 

  7. Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, van Ravenzwaay B (2008) Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol 82:151–157

    Article  PubMed  CAS  Google Scholar 

  8. Wang J, Zheng L, Wang S, Wang Y, Zhao X, Duan Y, Cui Y, Zhou M, Cai J, Gong S, Wang H, Hong F (2010) P38-Nrf-2 signaling pathway of oxidative stress in mice caused by nanoparticulate TiO2. Biol Trace Elem Res. doi:10.1007/s12011-010-8663-8

    Google Scholar 

  9. Cui YL, Liu HT, Zhou M, Duan YM, Li N, Gong XL, Hu RP, Hong MM, Hong FS (2011) Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles. J Biomed Mater Res A 96A:221–229

    Article  CAS  Google Scholar 

  10. Shin JA, Lee EJ, Seo SM, Kim HS, Kang JL, Park EM (2010) Nanosized titanium dioxide enhanced inflammatory responses in the septic brain of mouse. Neuroscience 165:445–454

    Article  PubMed  CAS  Google Scholar 

  11. Li N, Ma LL, Wang J, Zheng L, Liu J, Duan YM, Liu HT, Zhao XY, Wang SS, Wang H, Hong FS, Xie YN (2010) Interaction between nano-anatase TiO2 and liver DNA from mice in vivo. Nanoscale Res Lett 5:108–115

    Article  CAS  Google Scholar 

  12. Bhattacharya K, Davoren M, Boertz J, Schins RPF, Hoffmann E, Dopp E (2009) Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 6:17

    Article  PubMed  Google Scholar 

  13. Cui YL, Gong XL, Duan YM, Li N, Hu RP, Liu HT, Hong MM, Zhou M, Wang L, Wang H, Hong FS (2010) Hepatocyte apoptosis and its molecular mechanisms in mice caused by titanium dioxide nanoparticles. J Hazard Mater 183:874–880

    Article  PubMed  CAS  Google Scholar 

  14. Lai JCK, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW (2008) Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomed 3:533–545

    CAS  Google Scholar 

  15. Liu HT, Ma LL, Zhao JF, Liu J, Yan JY, Ruan J, Hong FS (2009) Biochemical toxicity of nano-anatase TiO2 particles in mice. Biol Trace Elem Res 129:170–180

    Article  PubMed  CAS  Google Scholar 

  16. Kim HW, Ahn EK, Jee BK, Yoon HK, Lee KH, Lim Y (2009) Nanoparticulate-induced toxicity and related mechanism in vitro and in vivo. J Nanopart Res 11:55–65

    Article  CAS  Google Scholar 

  17. Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH (2009) Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69:8784–8789

    Article  PubMed  CAS  Google Scholar 

  18. Ma LL, Zhao JF, Wang J, Liu J, Duan YM, Liu HT, Li N, Yan JY, Ruan J, Wang H, Hong FS (2009) The acute liver injury in mice caused by nano-anatase TiO2. Nanoscale Res Lett 4:1275–1285

    Article  PubMed  CAS  Google Scholar 

  19. Li N, Duan YM, Hong MM, Zheng L, Fei M, Zhao XY, Wang J, Cui YL, Liu HT, Cai JW, Gong SJ, Wang H, Hong FS (2010) Spleen injury and apoptotic pathway in mice caused by titanium dioxide nanoparticules. Toxicol Lett 195:161–168

    Article  PubMed  CAS  Google Scholar 

  20. Duan YM, Liu J, Ma LL, Li N, Liu HT, Wang J, Zheng L, Liu C, Wang XF, Zhao XY, Yan JY, Wang SS, Wang H, Zhang XG, Hong FS (2010) Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials 31:894–899

    Article  PubMed  CAS  Google Scholar 

  21. Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B (2006) Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. Environ Sci Technol 40:4346–4352

    Article  PubMed  CAS  Google Scholar 

  22. Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, Hester S, Lowry GV, Veronesi B (2007) Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Persp 115:1631–1637

    Article  CAS  Google Scholar 

  23. Wang JX, Liu Y, Jiao F, Lao F, Li W, Gu YQ, Li YF, Ge CC, Zhou GQ, Li B, Zhao YL, Chai ZF, Chen CY (2008) Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles. Toxicology 254:82–90

    Article  PubMed  CAS  Google Scholar 

  24. Wang JX, Chen CY, Liu Y, Jiao F, Li W, Lao F, Li YF, Li B, Ge CC, Zhou GQ, Gao YX, Zhao YL, Chai ZF (2008) Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 183:72–80

    Article  PubMed  CAS  Google Scholar 

  25. Ma L, Liu J, Li N, Wang J, Duan Y, Yan J, Liu H, Wang H, Hong F (2010) Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity. Biomaterials 31:99–105

    Article  PubMed  CAS  Google Scholar 

  26. Yang Z, Liu ZW, Allaker RP, Reip P, Oxford J, Ahmad Z, Ren G (2010) A review of nanoparticle functionality and toxicity on the central nervous system. J R Soc Interface 7:S411–S422

    Article  PubMed  CAS  Google Scholar 

  27. Shimizu M, Tainaka H, Oba T, Mizuo K, Umezawa M, Takeda K (2009) Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxicol 6:20

    Article  PubMed  Google Scholar 

  28. Takeda K, Suzuki KI, Ishihara A, Kubo-Irie M, Fujimoto R, Tabata M, Oshio S, Nihei Y, Ihara T, Sugamata M (2009) Nanoparticles transferred from pregnant mice to their offspring can damage the genital and cranial nerve systems. J Health Sci 55:95–102

    Article  CAS  Google Scholar 

  29. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  30. Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87–136

    Article  PubMed  CAS  Google Scholar 

  31. AT JRM (1993) NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats. Brain Res 604:273–282

    Article  Google Scholar 

  32. Lynch MA (1998) Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta? Prog Neurobiol 56:571–589

    Article  PubMed  CAS  Google Scholar 

  33. Hougaard KS, Jackson P, Jensen KA, Sloth JJ, Loschner K, Larsen EH, Birkedal RK, Vibenholt A, Boisen AMZ, Wallin H, Vogel U (2010) Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice. Part Fibre Toxicol 7:16

    Article  PubMed  Google Scholar 

  34. Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F (2010) Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials 31:8043–8050

    Article  PubMed  CAS  Google Scholar 

  35. Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3:431–443

    Article  PubMed  CAS  Google Scholar 

  36. Lynch MA (2002) Interleukin-1 beta exerts a myriad of effects in the brain and in particular in the hippocampus: analysis of some of these actions. Vitam Horm 64:185–219

    Article  PubMed  CAS  Google Scholar 

  37. Kelly A, Lynch A, Vereker E, Nolan Y, Queenan P, Whittaker E, O’Neill LA, Lynch MA (2001) The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect of IL-1 beta on long term potentiation. A role for JNK. J Biol Chem 276:45564–45572

    Article  PubMed  CAS  Google Scholar 

  38. Murray CA, Lynch MA (1998) Evidence that increased hippocampal expression of the cytokine interleukin-1 beta is a common trigger for age- and stress-induced impairments in long-term potentiation. J Neurosci 18:2974–2981

    PubMed  CAS  Google Scholar 

  39. Cunningham AJ, Murray CA, O’Neill LA, Lynch MA, O’Connor JJ (1996) Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett 203:17–20

    Article  PubMed  CAS  Google Scholar 

  40. Altman J, Bayer SA (1990) Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 301:365–381

    Article  PubMed  CAS  Google Scholar 

  41. Taupin P (2007) The hippocampus: neurotransmission and plasticity in the nervous system. Nova, New York, 94

    Google Scholar 

Download references

Acknowledgement

This work was supported by the Fundamental Research Funds for the Central Universities (WK2070000002, 2070000004, and 2070000008), The National Nature Science Foundations of China (30630057, 30670554/30670662, and 31070936). We confirm that we have no competing financial interests.

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Correspondence to Ming Wang.

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Gao, X., Yin, S., Tang, M. et al. Effects of Developmental Exposure to TiO2 Nanoparticles on Synaptic Plasticity in Hippocampal Dentate Gyrus Area: an In Vivo Study in Anesthetized Rats. Biol Trace Elem Res 143, 1616–1628 (2011). https://doi.org/10.1007/s12011-011-8990-4

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