Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • 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)

  • Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gasps. Int J Biomed Nanosci Nanotechnol 3(1–2):1–44

    Google Scholar 

  • 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):544–550

    Article  Google Scholar 

  • Bourin M (2015) Animal models for screening anxiolytic-like drug: a perspective. Dialogues Clin Neurosci 17(3):295–303

    Google Scholar 

  • Brown AP, Dinger N, Levine BS (2000) Stress produced by gavage administration in the rat. Lab Anim Sci 39(1):17–21

    Google Scholar 

  • Bystrzejewska-Piotrowska G, Golimowski J, Urban PL (2009) Nanoparticles: their potential toxicity, waste and environmental management. Waste Manag 29:2587–2595

    Article  Google Scholar 

  • Can A, Dao DT, Terrilliom CE, Piantodosi SC, Bhat S, Gould TD (2012) The tail suspension test. J Vis Exp 59:3769

    Google Scholar 

  • 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

    Article  Google Scholar 

  • Cowen PJ, Browning M (2015) What has serotonina to do with depression? World Psychiatry 14(2):158–160

    Article  Google Scholar 

  • Crowley JJ, Blendy JA, Lucki I (2005) Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test. Psychopharmacology 183(2):257–264

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Dudhani AR, Kosaraju SL (2010) Bioadhesive chitosan nanoparticles: preparation and characterization. Carbohydr Polym 81:243–251

    Article  Google Scholar 

  • 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):47e59

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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):5541–5551

    Article  Google Scholar 

  • 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):46643

    Article  Google Scholar 

  • Grillo R, Jesus MB, Fraceto LF (2018) Environmental impact f nanotechnology: analyzing the present for building the future. Front Environ Sci 6:1–3

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Handy R, Owen R, Valsami-Jones E (2008) The ecotoxicology of nanoparticles and nanomaterials: current status, knowledge gaps, challenges, and future needs. Ecotoxicology 17:315–325

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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):497–509

    Google Scholar 

  • 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

    Article  Google Scholar 

  • Hu X, Li D, Gao Y, Um L, Zhou Q (2016) Knowledge gaps between nanotoxicological research and nanomaterial safety. Environ Int 94:8–23

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Jacob J, Haponiuk JT, Thomas S, Gopi S (2018) Biopolymer based nanomaterials in drug delivery systems: a review. Mater Today Chem 9:43–55

    Article  Google Scholar 

  • 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 

  • Karmakar A, Zhang Q, Zhang Y (2014) Neurotoxicity of nanoscale materials. J Food Drug Anal 22(1):147–160

    Article  Google Scholar 

  • 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 415:197–201

    Article  Google Scholar 

  • Kreuter J (2014) Drug delibery to the central nervous system by polymeric nanoparticles: what do we know? Adv Drug Deliv Rev 71:2–14

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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 

  • 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 ago

  • 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 109:1326–1332

    Google Scholar 

  • 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 

  • 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.

  • 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

    Article  Google Scholar 

  • 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):1011

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Mohanraj VJ, Chen Y (2006) Nanoparticles – a review. Trop J Pharm Res 5(1):561–573

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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):1330–1340

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Paliwal R, Palakurthi S (2014) Zein in controlled drug delivery and tissue engineering. J Control Release 189:108–122

    Article  Google Scholar 

  • 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 24:1725–1733

    Article  Google Scholar 

  • 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):103–110

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Saraiva ME, Soares Fortunato JM, Gavina C (2005) Oscilações do cortisol na depressão e sono/vigília. Rev Port Psicossomática 7:89–100

    Google Scholar 

  • Sosnik A, Menaker Raskin M (2015) Polymeric micelles in mucosal drug delivery: challenges towards clinical translation. Biotechnol Adv 33:1380–1392

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Tabatabaei SR, Moshrefi M, Askaripour M (2015) Prenatal exposure to silver nanoparticles causes depression like responses in mice. Indian J Pharm Sci 77(6):681–686

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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):322–328

    Article  Google Scholar 

  • Wang Y-F, Liu L, Xue X, Liang X-J (2017) Nanoparticle-based drug delivery systems: what can they really do in vivo? F1000Research 6:681

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

Download references

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

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).

Author information

Authors and Affiliations

  1. Post-graduation Program in Cerrado Natural Resource Conservation and Biological Research Laboratory, Instituto Federal Goiano–Urutaí Campus, Urutai, GO, Brazil

    Vinícius Silva Lima, Amanda Pereira da Costa Araújo & Guilherme Malafaia

  2. Post-graduation Program in Biotechnology and Biodiversity, Universidade Federal de Goiás, Goiania, GO, Brazil

    Abraão Tiago Batista Guimarães & Fernanda Neves Estrela

  3. Itaquera Campus, São Paulo, Brazil University, São Paulo, SP, Brazil

    Ives Charlie da Silva

  4. Faculty of Medicine São Leopoldo Mandic, Araras, SP, Brazil

    Nathalie Ferreira Silva de Melo

  5. Institute of Science and Technology of Sorocaba, São Paulo State University (UNESP), Sorocaba, SP, Brazil

    Leonardo Fernandes Fraceto

  6. Laboratório de Pesquisas Biológicas, Instituto Federal Goiano–Campus Urutaí, Rodovia Geraldo Silva Nascimento, 2,5 km, Zona Rural, Urutaí, GO, Brazil

    Guilherme Malafaia

Authors
  1. Vinícius Silva Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abraão Tiago Batista Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amanda Pereira da Costa Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernanda Neves Estrela
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ives Charlie da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathalie Ferreira Silva de Melo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leonardo Fernandes Fraceto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guilherme Malafaia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guilherme Malafaia.

Additional information

Responsible editor: Philippe Garrigues

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lima, V.S., Guimarães, A.T.B., da Costa Araújo, A.P. et al. Depression, anxiety-like behavior, and memory impairment in mice exposed to chitosan-coated zein nanoparticles. Environ Sci Pollut Res 26, 10641–10650 (2019). https://doi.org/10.1007/s11356-019-04536-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-04536-0

Keywords

Search

Navigation