Efeitos ansiolíticos das proteínas de Leishmania braziliensis em modelo animal de zebrafish
DOI:
https://doi.org/10.34024/rnc.2023.v31.14571Palavras-chave:
Proteínas, Ansiedade, Sistema Nervoso Central, LeishmaniaResumo
Introdução. A leishmaniose está entre as 22 doenças mais negligenciadas em todo o mundo. Pouco se fala das evidências do acometimento neurológico que a leishmaniose pode acometer, devido às ulcerações formadas na pele em curto e em longo prazo. Todavia, alguns autores já citam que a leishmania pode causar inflamação no sistema nervoso central, podendo desencadear processos neuropsicomportamentais como a ansiedade. Objetivo. O presente estudo enfoca a avaliação dos efeitos das proteínas totais de Leishmania no sistema nervoso central no modelo de Zebrafish. Método. Foram realizados, inicialmente, o cultivo da Leishmania para serem extraídas as proteínas totais pelos métodos de Sonicação e Bradford. Após a extração das proteínas totais, foram inoculados no peixe-zebra para a observação da sintomatologia ocasionada pela carga de proteínas, e, após os 7 dias de inoculação, realizamos os testes comportamentais (Campo Aberto e Claro & Escuro). Resultados. Os peixes tratados com proteína de Leishmania apresentaram várias alterações cutâneas, bem como alterações comportamentais. Os testes comportamentais de campo aberto mostram um número de cruzamentos altos em relação ao grupo controle. No teste claro e escuro, o peixe-zebra teve uma permanência maior no campo claro, sendo observada uma ação ansiolítica nos animais que receberam a administração das proteínas. Conclusão. As proteínas totais de Leishmania podem, sim, ter uma ação ansiolítica no modelo de zebrafish.
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Molyneux DH, Savioli L, Engels D. Neglected tropical diseases: progress towards addressing the chronic pandemic. Lancet 2017;389:312-25. https://doi.org/10.1016/S0140-6736(16)30171-4
Global Health Observatory. Leishmaniasis. Geneva: World Health Organization; 2020 (accessed May 2021). Available in: https://www.who.int/gho/neglected_diseases/leishmaniasis/en/
Oliveira VdC, Boechat VC, Mendes Junior AAV, Madeira MdF, Ferreira LC, Figueiredo FB, et al. Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations. PLoS ONE 2017;12:e0175588. https://doi.org/10.1371/journal. pone.0175588
Portes A, Giestal-de-Araujo E, Fagundes A, Pandolfo P, Geraldo AS, Lira MLF, et al. Leishmania amazonensis infection induces behavioral alterations and modulates cytokine and neurotrophin production in the murine cerebral cortex. J Neuroimmunol 2016;301:65-73. https://doi.org/10.1016/j.jneuroim.2016.11.003
Brundin L, Erhardt S, Bryleva EY, Achtyes ED, Postolache TT. The role of inflammation in suicidal behaviour. Acta Psychiatr Scand 2015;132:192-203. https://doi.org/10.1111/acps.12458
Debnath M, Berk M. Th17 pathway-mediated immunopathogenesis of schizophrenia: mechanisms and implications. Schizophr Bull 2014;40:1412-21. https://doi.org/10.1093/schbul/sbu049
Notarangelo FM, Wilson EH, Horning KJ, Thomas MA, Harris TH, Fang Q, et al. Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia. Schizophr Res 2014;152:261-7. https://doi.org/10.1016/j.schres.2013.11.011
Ramos PK, Brito MV, Silveira FT, Salgado CG, De Souza W, Picanço-Diniz CW, et al. In vitro cytokines profile and ultrastructural changes of microglia and macrophages following interaction with Leishmania. Parasitology 2014;141:1052-63. https://doi.org/10.1017/S0031182014000274
Honório Jr JER, Vasconcelos GS, Rodrigues FT, Sena Filho JG, Barbosa-Filho JM, Aguiar CC, et al. Monocrotaline: histological damage and oxidant activity in brain areas of mice. Oxid Med Cell Longev 2012;2012:697541. https://doi.org/10.1155/2012/697541
Gerlai R, Lahav M, Guo S, Rosenthal A. Drinks like a fish: zebra fish (Danio rerio) as a behavior genetic model to study alcohol effects. Pharmacol Biochem Behav 2000;67:773-82. https://doi.org/10.1016/s0091-3057(00)00422-6
Lenth RV. Java applests for power and sample size. [Computer Software]. 2006; (accessed in 01/13/2020). Avaiable in: https://www.stat.uiowa.edu/~rlenth/Power
Almeida RS, Klotzle MC, Figueiredo Pinto AC. Composição do conselho de Administração no setor de energia elétrica do Brasil. R Admin UNIMEP 2013;11:156-80. http://www.raunimep.com.br/ojs/index.php/rau/article/view/509
Magalhães FEA, Batista FLA, Lima LMG, Abrante IA, Batista FLA, Abrante IA, et al. Adult Zebrafish (Danio rerio) As a Model for the Study of Corneal Antinociceptive Compounds. Zebrafish 2018;15:566-74. https://doi.org/10.1089/zeb.2018.1633
Tatem KS, Quinn JL, Phadke A, Yu Q, Gordish-Dressman H, Nagaraju K. Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases. J Vis Exp 2014;91:51785. https://doi.org/10.3791/51785
Magalhães FEA, de Sousa CÁPB, Santos SAAR, Menezes RB, Batista FLA, Abreu ÂO, et al. Adult Zebrafish (Danio rerio): An Alternative Behavioral Model of Formalin-Induced Nociception. Zebrafish 2017;14:422-9. https://doi.org/10.1089/zeb.2017.1436
Maximino C. Serotonin in the nervous system of vertebrates. In: Serotonin and Anxiety. New York: Springer; 2012; pp15-36. https://link.springer.com/chapter/10.1007/978-1-4614-4048-2_2
Arango Duque G, Descoteaux A. Leishmania survival in the macrophage: where the ends justify the means. Curr Opin Microbiol 2015;26:32-40. https://doi.org/10.1016/j.mib.2015.04.007
Gouveia JR A, Zampieri RA, Ramos LA, Silva EF, Mattioli R, Morato S. Preference of goldfish (Carassius auratus) for dark places. Rev Etol 2005;7:63-6. http://pepsic.bvsalud.org/scielo.php?script=sci_arttext&pid=S1517-28052005000200002&lng=pt&nrm=iso
Amiri-Dashatan N, Rezaei-Tavirani M, Ahmadi N. A quantitative proteomic and bioinformatics analysis of proteins in metacyclogenesis of Leishmania tropica. Acta Trop 2020;202:105227. https://doi.org/10.1016/j.actatropica.2019.105227
Castro Neto AL, Brito ANALM, Rezende AM, Magalhães FB, de Melo Neto OP. In silico characterization of multiple genes encoding the GP63 virulence protein from Leishmania braziliensis: identification of sources of variation and putative roles in immune evasion. BMC Genomics 2019;20:118. https://doi.org/10.1186/s12864-019-5465-z
Laranjeira-Silva MF, Wang W, Samuel TK, Maeda FY, Michailowsky V, Hamza I, et al. A MFS-like plasma membrane transporter required for Leishmania virulence protects the parasites from iron toxicity. PLoS Pathog 2018;14:e1007140. https://doi.org/10.1371/journal.ppat.1007140
Scorza BM, Carvalho EM, Wilson ME. Cutaneous Manifestations of Human and Murine Leishmaniasis. Int J Mol Sci 2017;18:1296. https://doi.org/10.3390/ijms18061296
Pires M, Wright B, Kaye PM, da Conceição V, Churchill RC. The impact of leishmaniasis on mental health and psychosocial well-being: A systematic review. PLOS ONE 2019;14:e0223313. https://doi.org/10.1371/journal.pone.0223313
Paul CD, Devine A, Bishop K, Xu Q, Wulftange WJ, Burr H, et al. Human macrophages survive and adopt activated genotypes in living zebrafish. Sci Rep 2019;9:1759. https://doi.org/10.1038/s41598-018-38186-y
Ellett F, Lieschke GJ. Zebrafish as a model for vertebrate hematopoiesis. Curr Opin Pharmacol 2010;10:563-70. https://doi.org/10.1016/j.coph.2010.05.004
Oosterhof N, Boddeke E, van Ham TJ. Immune cell dynamics in the CNS: Learning from the zebrafish. Glia 2015;63:719-35. https://doi.org/10.1002/glia.22780
Kalueff AV, Echevarria DJ, Stewart AM. Gaining translational momentum: More zebrafish models for neuroscience research. Progr NeuroPsychopharmacol Biol Psychiatr 2014;55:1-6. https://doi.org/10.1016/j.pnpbp.2014.01.022
Stewart AM, Ullmann JF, Norton WH, Parker MO, Brennan CH, Gerlai R, et al. Molecular psychiatry of zebrafish. Mol Psychiatry 2015;20:2-17. https://doi.org/10.1038/mp.2014.128
Khan KM, Collier AD, Meshalkina DA, Kysil EV, Khatsko SL, Kolesnikova T, et al. Zebrafish models in neuropsychopharmacology and CNS drug discovery. Br J Pharmacol 2017;174:1925-44. https://doi.org/10.1111/bph.13754
Carvalho TS, Cardoso PB, Santos-Silva M, Lima-Basto S, Luz WL, Assad H, et al. Oxidative Stress Mediates Anxiety-Like Behavior Induced by High Caffeine Intake in Zebrafish: Protective Effect of Alpha-Tocopherol. Oxid med cell longev 2019;2019:9. https://doi.org/10.1155/2019/8419810
Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 2009;29:247-64. https://doi.org/10.1016/j.iac.2009.02.002
Stelow E. Behavior as Illness Indicator. Vet Clin North Am Small Anim Pract 2018;48:9-10. https://doi.org/10.1016/j.cvsm.2017.12.002
Travi B, Rey-Ladino J, Saravia NG. Behavior of Leishmania braziliensis s.l. in golden hamsters: evolution of the infection under different experimental conditions. J Parasitol 1988;74:1059-62. https://doi.org/10.2307/3282237
Hussain A, Audira G, Malhotra N, Uapipatanakul B, Chen JR, Lai YH, et al. Multiple Screening of Pesticides Toxicity in Zebrafish and Daphnia Based on Locomotor Activity Alterations. Biomolecules 2020;10:1224. https://doi.org/10.3390/biom10091224
Ferreira MKA, da Silva AW, Silva FCO, Vieira Neto AE, Campos AR, Santos SAAR, et al. Anxiolytic-like effect of chalcone N-{4'[(2E)-3-(3-nitrophenyl)-1-(phenyl)prop-2-en-1-one]} acetamide on adult zebrafish (Danio rerio): Involvement of the 5-HT system. Biochem Biophys Res Commun 2020;526:505-11. https://doi.org/10.1016/j.bbrc.2020.03.129.
Gugliandolo E, Palma E, Peritore AF, Siracusa R, D'Amico R, Fusco R, et al. Effect of Artesunate on Leishmania Amazonesis Induced Neuroinflammation and Nociceptive Behavior in Male Balb/C Mice. Animals (Basel) 2020;10:557. https://doi.org/10.3390/ani10040557
Rosemberg DB, Rico EP, Mussulini BHM, Piato ÂL, Calcagnotto ME, Bonan CD, et al. Differences in Spatio-Temporal Behavior of Zebrafish in the Open Tank Paradigm after a Short-Period Confinement into Dark and Bright Environments. PLoS ONE 2011;6:e19397. https://doi.org/10.1371/journal.pone.0019397
Serra EL, Medalha CC, Mattioli R. Natural preference of zebrafish (Danio rerio) for a dark environment. Braz J Med Biol Res 1999;32: 1551-3. https://doi.org/10.1590/S0100-879X1999001200016
Osorio Y, Rodriguez LD, Bonilla DL, Peniche AG, Henao H, Saldarriaga O, et al. Congenital transmission of experimental leishmaniasis in a hamster model. Am J Trop Med Hyg 2012;86:812-20. https://doi.org/10.4269/ajtmh.2012.11-0458
Brito TM. Validação da preferência claro/escuro como modelo comportamental de ansiedade no Carassius auratus (peixe dourado) (Dissertação). Ribeirão Preto: Universidade de São Paulo; 2011. https://doi.org/10.11606/D.59.2011.tde-29022012-092339
Magno LD, Fontes A, Gonçalves BM, Gouveia A Jr. Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): Waterborne administration. Pharmacol Biochem Behav 2015;135:169-76. https://doi.org/10.1016/j.pbb.2015.05.014
Dahlén A, Wagle M, Zarei M, Guo S. Heritable natural variation of light/dark preference in an outbred zebrafish population. J Neurogenet 2019;33:199-208. https://doi.org/10.1080/01677063.2019.1663846
Gebauer DL, Pagnussat N, Piato ÂL, Schaefer IC, Bonan CD, Lara DR. Effects of anxiolytics in zebrafish: Similarities and differences between benzodiazepines, buspirone and ethanol. Pharmacol Biochem Behav 2011;9:480-6. https://doi.org/10.1016/j.pbb.2011.04.021
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Copyright (c) 2023 Natália Sousa de Sousa, Rayssa Mirelle Campos Gurgel, Pedro de Freitas Santos Manzi de Souza, Dara da Silva Mesquita, Roberto Nicolete, José Eduardo Ribeiro Honório Júnior

Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Aceito: 2023-03-08
Publicado: 2023-03-29