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Environmental Science and Pollution Research

, Volume 26, Issue 11, pp 10641–10650 | Cite as

Depression, anxiety-like behavior, and memory impairment in mice exposed to chitosan-coated zein nanoparticles

  • Vinícius Silva Lima
  • Abraão Tiago Batista Guimarães
  • Amanda Pereira da Costa Araújo
  • Fernanda Neves Estrela
  • Ives Charlie da Silva
  • Nathalie Ferreira Silva de Melo
  • Leonardo Fernandes Fraceto
  • Guilherme MalafaiaEmail author
Research Article
  • 259 Downloads

Abstract

The advent of biotechnology provided the synthesis of nanoproducts with diverse applications in the field of medicine, agriculture, food, among others. However, the toxicity of many nanoparticles (NP) currently used, which can penetrate natural systems and impact organisms, is not known. Thus, in this study, we evaluated whether the short exposure (5 days) to low concentrations of chitosan-coated zein nanoparticles (ZNP-CS) (0.2 ng/kg, 40 ng/kg, and 400.00 ng/kg) was capable of causing behavioral alterations compatible with cognitive deficit, as well as anxiety and depression-like behavior in Swiss mice. However, we observed an anxiogenic effect in the animals exposed to the highest ZNP-CS concentration (400.00 ng/kg), without locomotor alterations suggestive of sedation or hyperactivity in the elevated plus maze (EPM) test. We also observed that the ZNP-CS caused depressive-like behavior, indicated by the longer immobile time in the tail suspension test and the animals exposed to ZNP-CS presented deficit in recognition of the new object, not related to locomotor alteration in this test. To the best of our knowledge, this is the first report of the neurotoxicity of ZNP in a mammal animal model, contributing to the biological safety assessment of these nanocomposites.

Keywords

Neurotoxicity Engineered nanomaterials Mammalian Environmental toxicology 

Notes

Acknowledgements

The authors are grateful to CNPq and Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG, Brazil) for granting the scholarship to the student who developed the study.

Funding information

This study was financially supported by the Brazilian National Research Council (CNPq) (Brazilian research agency) (Proc. N. 467801/2014-2) and Goiano Federal Institute (Proc. No. 23218.000286/2017-21).

References

  1. Bali YA, Ba-Mhamed S, Bennis M (2017) Behavioral and Immunohistochemical study of the effects of subchronic and chronic exposure to glyphosate in mice. Front Behav Neurosci 11(146)Google Scholar
  2. Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gasps. Int J Biomed Nanosci Nanotechnol 3(1–2):1–44Google Scholar
  3. Bouayed J, Bohn T, Tybl E, Kiemer AK, Soulimani R (2012) Benzo[α]pyrene-induced anti-depressive-like behaviour in adult female mice: role of monoaminergic systems. Basic Clin Pharmacol Toxicol 110(6):544–550CrossRefGoogle Scholar
  4. Bourin M (2015) Animal models for screening anxiolytic-like drug: a perspective. Dialogues Clin Neurosci 17(3):295–303Google Scholar
  5. Brown AP, Dinger N, Levine BS (2000) Stress produced by gavage administration in the rat. Lab Anim Sci 39(1):17–21Google Scholar
  6. Bystrzejewska-Piotrowska G, Golimowski J, Urban PL (2009) Nanoparticles: their potential toxicity, waste and environmental management. Waste Manag 29:2587–2595CrossRefGoogle Scholar
  7. Can A, Dao DT, Terrilliom CE, Piantodosi SC, Bhat S, Gould TD (2012) The tail suspension test. J Vis Exp 59:3769Google Scholar
  8. Cardoso LS, Estrela FN, Chagas TQ, da Silva WAM, Costa DRO, Pereira I, Vaz BG, Rodrigues ASL, Malafaia G (2018 Mar) The exposure to water with cigarette residue changes the anti-predator response in female Swiss albino mice. Environ Sci Pollut Res Int 25(9):8592–8607.  https://doi.org/10.1007/s11356-017-1150-4 CrossRefGoogle Scholar
  9. Cowen PJ, Browning M (2015) What has serotonina to do with depression? World Psychiatry 14(2):158–160CrossRefGoogle Scholar
  10. Crowley JJ, Blendy JA, Lucki I (2005) Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test. Psychopharmacology 183(2):257–264CrossRefGoogle Scholar
  11. Cunha MP, Machado DG, Bettio LE, Capra JC, Rodrigues AL (2008) Interaction of zinc with antidepressants in the tail suspension test. Prog Neuro-Psychopharmacol Biol Psychiatry 32(8):1913–1920.  https://doi.org/10.1016/j.pnpbp.2008.09.006 CrossRefGoogle Scholar
  12. Dudhani AR, Kosaraju SL (2010) Bioadhesive chitosan nanoparticles: preparation and characterization. Carbohydr Polym 81:243–251CrossRefGoogle Scholar
  13. Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31(1):47e59CrossRefGoogle Scholar
  14. Estrela DC, da Silva WA, Guimarães AT, de Oliveira Mendes B, da Silva Castro AL, da Silva Torres IL, Malafaia G (2015) Predictive behaviors for anxiety and depression in female Wistar rats subjected to cafeteria diet and stress. Physiol Behav 151:252–263.  https://doi.org/10.1016/j.physbeh.2015.07.016 CrossRefGoogle Scholar
  15. Garner KL, Suh S, Keller AA (2017) Assessing the risk of engineered nanomaterials in the environment: development and application of the nanoFate model. Environ Sci Technol 51(10):5541–5551CrossRefGoogle Scholar
  16. Ghalei S, Asadi H, Ghalei B (2018) Zein nanoparticle-embedded electrospun PVA nanofibers as wound dressing for topical delivery of anti-inflammatory diclofenac. J Appl Polym Sci 135(33):46643CrossRefGoogle Scholar
  17. Grillo R, Jesus MB, Fraceto LF (2018) Environmental impact f nanotechnology: analyzing the present for building the future. Front Environ Sci 6:1–3CrossRefGoogle Scholar
  18. Guimarães ATB, de Oliveira Ferreira R, de Lima Rodrigues AS, Malafaia G (2017) Memory and depressive effect on male and female Swiss mice exposed to tannery effluent. Neurotoxicol Teratol 61:123–127.  https://doi.org/10.1016/j.ntt.2017.03.003 CrossRefGoogle Scholar
  19. Handy R, Owen R, Valsami-Jones E (2008) The ecotoxicology of nanoparticles and nanomaterials: current status, knowledge gaps, challenges, and future needs. Ecotoxicology 17:315–325CrossRefGoogle Scholar
  20. Hansen SF, Heggelund LR, Besora PR, Mackevica A, Boldrin A, Baun A (2016) Nanoproducts - what is actually available to European consumers? Environ Sci Nano 3:169–180.  https://doi.org/10.1039/C5EN00182J CrossRefGoogle Scholar
  21. Hritcu L, Stefan M, Ursu L, Neagu A, Mihasan M, Tartau L et al (2011) Exposure to silver nanoparticles induces oxidative stress and memory deficits in laboratory rats. Cen Euro J Biol 6(4):497–509Google Scholar
  22. Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F (2010 Nov) Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials 31(31):8043–8050.  https://doi.org/10.1016/j.biomaterials.2010.07.011 CrossRefGoogle Scholar
  23. Hu X, Li D, Gao Y, Um L, Zhou Q (2016) Knowledge gaps between nanotoxicological research and nanomaterial safety. Environ Int 94:8–23CrossRefGoogle Scholar
  24. Irache JM, González-Navarro CJ (2017) Zein nanoparticles as vehicles for oral delivery purposes. Nanomed (Lond) 12(11):1209–1211.  https://doi.org/10.2217/nnm-2017-0075 CrossRefGoogle Scholar
  25. Jacob J, Haponiuk JT, Thomas S, Gopi S (2018) Biopolymer based nanomaterials in drug delivery systems: a review. Mater Today Chem 9:43–55CrossRefGoogle Scholar
  26. Jain A, Sharma G, Kushwah V, Ghoshal G, Jain A, Singh B, Shivhare US, Jain S, Katare OP (2018) Beta carotene-loaded zein nanoparticles to improve the biopharmaceutical attributes and to abolish the toxicity of methotrexate: a preclinical study for breast cancer. Artif Cells Nanomed Biotechnol 23:1–11.  https://doi.org/10.1080/21691401.2018.1428811 Google Scholar
  27. Karmakar A, Zhang Q, Zhang Y (2014) Neurotoxicity of nanoscale materials. J Food Drug Anal 22(1):147–160CrossRefGoogle Scholar
  28. Karolewicz B, Paul IA (2001) Group housing of mice increases immobility and antidepressant sensitivity in the forced swim and tail suspension tests. Eur J Pharmacol 415:197–201CrossRefGoogle Scholar
  29. Kreuter J (2014) Drug delibery to the central nervous system by polymeric nanoparticles: what do we know? Adv Drug Deliv Rev 71:2–14CrossRefGoogle Scholar
  30. Lai LF, Guo H (2011 Feb 14) Preparation of new 5-fluorouracil-loaded zein nanoparticles for liver targeting. Int J Pharm 404(1–2):317–323.  https://doi.org/10.1016/j.ijpharm.2010.11.025 CrossRefGoogle Scholar
  31. Lima IA, Khalil NM, Tominaga TT, Lechanteur A, Sarmento B, Mainardes RM (2018 May) Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid. Artif Cells Nanomed Biotechnol. 29:1–10.  https://doi.org/10.1080/21691401.2018.1477788 Google Scholar
  32. Luo Y, Wang Q (2014) Zein-Based Micro- and Nano-Particles for Drug and Nutrient Delivery: A review. J Appl Polymer Sci 131(16). 15 agoGoogle Scholar
  33. Malafaia G, Estrela DC, Silva WAM, Guimarães ATB, Mendes BO, Rodrigues ASL, Menezes IPP (2015) Toxicity study in mice fed with corn produced in soil containing tannery sludge vermicompost and irrigated with domestic wastewater. Curr Sci 109:1326–1332Google Scholar
  34. Matsoukas T, Desai T, Lee K (2015) Engineered nanoparticle and their applications. J Nanomater 651273:2–2.  https://doi.org/10.1155/2015/651273 Google Scholar
  35. Melo NF, de Macedo CG, Bonfante R, Abdalla HB, da Silva CM, Pasquoto T, de Lima R, Fraceto LF, Clemente-Napimoga JT, Napimoga MH (2016) 15d-PGJ2-loaded solid lipid nanoparticles: physicochemical characterization and evaluation of pharmacological effects on inflammation. PLoS One 11(8):e0161796.  https://doi.org/10.1371/journal.pone.0161796.eCollection2016.
  36. Melo NFS, Campos EVR, Franz-Montan M, Paula E, Silva CMGD, Maruyama CR, Stigliani TP, Lima R, Araújo DR, Fraceto LF (2018 Jun 1) Characterization of Articaine-loaded poly(ε-caprolactone) Nanocapsules and solid lipid nanoparticles in hydrogels for topical formulations. J Nanosci Nanotechnol 18(6):4428–4438.  https://doi.org/10.1166/jnn.2018.15235 CrossRefGoogle Scholar
  37. Mendes BO, Guimarães ATB, Castro ACF, Silva BC, Barbosa CC, Barbosa JJ, Souza JM, Rabelo LM, Souza MR, Moreira MG, Mazzei ND, Santos JA, Ferreira RO, Silva WA, Malafaia G (2016) Dermal exposure to tannery effluent did not Alter predictive behavior for depression in male Swiss mice. JSM Anxiety Depress 1(3):1011Google Scholar
  38. Mendes BO, Rabelo LM, Silva E (2017 Aug) BC, de Souza JM, da Silva Castro AL, da Silva AR, de Lima Rodrigues AS, Malafaia G. Mice exposure to tannery effluents changes their olfactory capacity, and their response to predators and to the inhibitory avoidance test. Environ Sci Pollut Res Int 24(23):19234–19248.  https://doi.org/10.1007/s11356-017-9504-5 CrossRefGoogle Scholar
  39. Mesak C, Sampaio DMDR, Ferreira RO, Mendes BO, Rodrigues ASL, Malafaia G (2018 Nov) The effects of predicted environmentally relevant concentrations of ZnO nanoparticles on the behavior of Gallus gallus domesticus (Phasianidae) chicks. Environ Pollut 242(Pt B):1274–1282.  https://doi.org/10.1016/j.envpol.2018.08.004 CrossRefGoogle Scholar
  40. Mohanraj VJ, Chen Y (2006) Nanoparticles – a review. Trop J Pharm Res 5(1):561–573Google Scholar
  41. Moreno LCGEI, Puerta E, Suárez-Santiago JE, Santos-Magalhães NS, Ramirez MJ, Irache JM (2017 Jan 30) Effect of the oral administration of nanoencapsulated quercetin on a mouse model of Alzheimer's disease. Int J Pharm 517(1–2):50–57.  https://doi.org/10.1016/j.ijpharm.2016.11.061 CrossRefGoogle Scholar
  42. Oliveira JL, Campos EVR, Pereira AES, Pasquoto T, Lima R, Grillo R, Andrade DJ, Santos FA, Fraceto LF (2018) Zein nanoparticles as eco-friendly carrier systems for botanical repellents aiming sustainable agriculture. J Agric Food Chem 66(6):1330–1340CrossRefGoogle Scholar
  43. Ozel RE, Wallace KN, Andreescu S (2011 Jun 10) Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos. Anal Chim Acta 695(1–2):89–95.  https://doi.org/10.1016/j.aca.2011.03.057 CrossRefGoogle Scholar
  44. Paliwal R, Palakurthi S (2014) Zein in controlled drug delivery and tissue engineering. J Control Release 189:108–122CrossRefGoogle Scholar
  45. Park C-E, Park D-J, Kim B-K (2015) Effects of a chitosan coating on properties of retinol-encapsulated zein nanoparticles. Food Sci Biotechnol 24:1725–1733CrossRefGoogle Scholar
  46. Penalva R, Gonzáles-Navarro CJ, Gamazo C, Esparza I, Irache JM (2017) Zein nanoparticles for oral delivery of quercetin: pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia. Nanomedicine 13(10):103–110CrossRefGoogle Scholar
  47. Rabelo LM, Costa E Silva B, de Almeida SF, da Silva WA, de Oliveira Mendes B, Guimarães AT, da Silva AR, da Silva Castro AL, de Lima Rodrigues AS, Malafaia G (2016 May-Jun) Memory deficit in Swiss mice exposed to tannery effluent. Neurotoxicol Teratol 55:45–49.  https://doi.org/10.1016/j.ntt.2016.03.007 CrossRefGoogle Scholar
  48. Ristroph KD, Astete CE, Bodoki E, Sabliov CM (2017 Dec 19) Zein nanoparticles uptake by hydroponically grown soybean plants. Environ Sci Technol 51(24):14065–14071.  https://doi.org/10.1021/acs.est.7b03923 CrossRefGoogle Scholar
  49. Saraiva ME, Soares Fortunato JM, Gavina C (2005) Oscilações do cortisol na depressão e sono/vigília. Rev Port Psicossomática 7:89–100Google Scholar
  50. Sosnik A, Menaker Raskin M (2015) Polymeric micelles in mucosal drug delivery: challenges towards clinical translation. Biotechnol Adv 33:1380–1392CrossRefGoogle Scholar
  51. Souza JM, Rabelo LM, de Faria DBG, Guimarães ATB, da Silva WAM, Rocha TL, Estrela FN, Chagas TQ, de Oliveira Mendes B, Malafaia G (2018) The intake of water containing a mix of pollutants at environmentally relevant concentrations leads to defensive response deficit in male C57Bl/6J mice. Sci Total Environ 628-629:186–197.  https://doi.org/10.1016/j.scitotenv.2018.02.040 CrossRefGoogle Scholar
  52. Tabatabaei SR, Moshrefi M, Askaripour M (2015) Prenatal exposure to silver nanoparticles causes depression like responses in mice. Indian J Pharm Sci 77(6):681–686CrossRefGoogle Scholar
  53. Takada T, Yoneda N, Hirano T, Yanai S, Yamamoto A, Mantani Y, Yokoyama T, Kitagawa H, Tabuchi Y, Hoshi N (2018) Verification of the causal relationship between subchronic exposures to dinotefuran and depression-related phenotype in juvenile mice. J Vet Med Sci 80(4):720–724.  https://doi.org/10.1292/jvms.18-0022 CrossRefGoogle Scholar
  54. Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2(2):322–328CrossRefGoogle Scholar
  55. Wang Y-F, Liu L, Xue X, Liang X-J (2017) Nanoparticle-based drug delivery systems: what can they really do in vivo? F1000Research 6:681CrossRefGoogle Scholar
  56. You R, Ho YS, Hung CH, Liu Y, Huang CX, Chan HN, Ho SL, Lui SY, Li HW, Chang RC (2018) Silica nanoparticles induce neurodegeneration-like changes in behavior, neuropathology, and affect synapse through MAP K activation. Part Fibre Toxicol 15(1):28.  https://doi.org/10.1186/s12989-018-0263-3. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Vinícius Silva Lima
    • 1
  • Abraão Tiago Batista Guimarães
    • 2
  • Amanda Pereira da Costa Araújo
    • 1
  • Fernanda Neves Estrela
    • 2
  • Ives Charlie da Silva
    • 3
  • Nathalie Ferreira Silva de Melo
    • 4
  • Leonardo Fernandes Fraceto
    • 5
  • Guilherme Malafaia
    • 1
    • 6
    Email author
  1. 1.Post-graduation Program in Cerrado Natural Resource Conservation and Biological Research LaboratoryInstituto Federal Goiano–Urutaí CampusUrutaiBrazil
  2. 2.Post-graduation Program in Biotechnology and BiodiversityUniversidade Federal de GoiásGoianiaBrazil
  3. 3.Itaquera Campus, São PauloBrazil UniversitySão PauloBrazil
  4. 4.Faculty of Medicine São Leopoldo MandicArarasBrazil
  5. 5.Institute of Science and Technology of SorocabaSão Paulo State University (UNESP)SorocabaBrazil
  6. 6.Laboratório de Pesquisas BiológicasInstituto Federal Goiano–Campus UrutaíUrutaíBrazil

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