Sobre o Autismo, Neuroinflamação e Modelos Animais para o Estudo de Autismo:

Uma Revisão

  • Maria Martha Bernardi Neurocientista, Doutora, Professor adjunto da Faculdade de Pedagogia do Centro de Ciências e Humanidades, Universidade Presbiteriana Mackenzie, São Paulo, SP, Brasil, e pesquisadora do Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo- SP, Brasil.
  • Thiago Berti Kirsten Biólogo, Mestre, Doutorando do Programa de Pós-graduação em Patologia Experimental e Comparada do Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo-SP, Brasil.
  • Mácio Oliveira Trindade Bacharel em Educação, Mestrando do Programa de Educação, Arte e História da Cultura da Universidade Presbiteriana Mackenzie, Professor Assistente do Centro de Ciências e Humanidades da Universidade Presbiteriana Mackenzie, São Paulo-SP, Brasil.
Palavras-chave: Autismo, Comportamento Animal, ranstornos do Desenvolvimento Infantil, Modelos Animais

Resumo

Este artigo busca mostrar a relevância de modelos animais no estudo da síndrome autista por meio de revisão da literatura. Embora eles pos­sam ser discutidos pela sua limitação, a contribuição no entendimento da síndrome e possibilidades de procedimentos que não são possíveis em humanos por razões éticas permite desvendar alguns aspectos dessa desordem. O autismo é um distúrbio psiquiátrico de desenvolvimento que se caracteriza por alterações comportamentais desde a infância, tais como prejuízo na comunicação, na interação social, além de mo­vimentos repetitivos e estereotipados e dificuldades de aprendizado. Esses sintomas podem ser severos ou moderados e/ou parciais, além de nenhuma manifestação ser exclusiva desse transtorno, o que dificulta o diagnóstico. Os achados neuroanatômico-funcionais são inespecí­ficos, assim como os estudos genéticos. Além da eventual predispo­sição genética, fatores ambientais, como a neuroinflamação, podem aumentar a incidência do autismo. A corrente de estudos atribuindo distúrbios mentais, inclusive o autismo, a alterações imunes se apóia cada vez mais em inúmeras publicações recentes, envolvendo acha­dos neuroimunes e desenvolvimento de diversos modelos animais. O presente trabalho realizou uma revisão sobre o autismo, discutindo a contribuição dos modelos animais para o estudo desta síndrome, além de discorrer sobre a participação da neuroinflamação como um fator associado à gênese desta patologia.

Métricas

Carregando métricas...

Referências

Camargo SPH, Bosa CA. Competência social, inclusão escolar e autismo. Psicol Soc 2009;21:65-74.

Manual de diagnóstico e estatística de transtornos mentais (DSM IV) [endereço na Internet]. Porto Alegre: Artes Médicas. (atualizado em: agosto/2011; citado em: agosto/2011). Disponível em: http://virtualpsy.locaweb.com.br/dsm.php.

Bugalho P, Correa B, Viana-Baptista M. Role of the cerebellum in cognitive and behavioural control: scientific basis and investigation models. Acta Med Port 2006;19:257-67.

Machado MG, Oliveira HA, Cipolotti R, Santos CA, de Oliveira EF, Donald RM, et al. Anatomical and functional abnormalities of central nervous system in autistic disorder: a MRI and SPECT study. Arq Neuropsiquiatr 2003; 61:957-61. http://dx.doi.org/10.1590/S0004-282X2003000600013

Libbey JE, Sweeten TL, McMahon WM, Fujinami RS. Autistic disorder and viral infections. J Neurovirol 2005;11:1-10. http://dx.doi.org/10.1080/13550280590900553

Klin A, Mercadante MT. [Autism and the pervasive developmental disorders]. Rev Bras Psiquiatr 2006;28(Suppl 1):S1-2. http://dx.doi.org/10.1590/S1516-44462006000500001 http://dx.doi.org/10.1590/S151644462006000500002

Classificação dos transtornos mentais e do comportamento da CID-10 [endereço na Internet]. Porto Alegre: Artes Médicas. (atualizado em agosto/2011; citado em: agosto/2011). Disponível em: http://www.datasus.gov.br/cid10/v2008/cid10.htm.

Fombonne E. Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry 2005;66 (Suppl 10):3-8.

Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009;65:591-8. http://dx.doi.org/10.1203/PDR.0b013e31819e7203

Theoharides TC, Kempuraj D, Redwood L. Autism: an emerging ‘neuroimmune disorder’ in search of therapy. Expert Opin Pharmacother 2009;10:2127-43. http://dx.doi.org/10.1517/14656560903107789

Wing L. Wing autistic disorder interview checklist (WADIC). In: Rapin I, editor. Preschool children with inadequate communication Developmental language disorder, autism, low IQ. London: Mac Keith Press, 1996, p.247-51.

Ajuriahuerra J. Las Psicosis Infantiles. Manual de Psiquiatria Infantil. Barcelona: Toray-Masson; 1977, p.673-731.

Kanner L. Autistic disturbances of affective contact. The nervous child 1943;2:217-50.

Eisenberg L, Kanner L. Childhood schizophrenia; symposium, 1955. VI. Early infantile autism, 1943-55. Am J Orthopsychiatry 1956;26:556-66. http://dx.doi.org/10.1111/j.1939-0025.1956.tb06202.x

Klein M. On early infantile psychosis: the symbiotic and autistic syndromes. J Am Acad Child Psychiatry 1965; 4:554-68. http://dx.doi.org/10.1016/S0002-7138(09)62158-0

Klein M. Os progressos da psicanálise (Original publicado em 1932). Rio de Janeiro: Zahar, 1989, p.79-135.

Mahler MD. On human symbiosis and the vicissitudes of individuation: Infantile psychosis. New York: International Universities; 1968, 271p.

Tustin F. Autistic states in children. London: Routledge and Kegan Paul; 1981, 272p.

Hobson P. Autism and the development of mind. Lawrence Erlbaum; 1993, 246p.

Baron-Cohen S. Theory of mind and autism: A fifteen year review. In: Baron-Cohen S, Tager-Flusberg H, Cohen DJ, editors. Understanding other minds: Perspectives from developmental cognitive neuroscience. London: Oxford University Press, 2000, p.3-20.

Assumpção JFB, Kuczynski E, Sprovieri MH, Farinha V. Reconhecimento facial e autismo. Arq Neuropsiquiatr 1999;57:944-9. http://dx.doi.org/10.1590/S0004-282X1999000600008

Hermelin B, O’Connor N. Psychological experiments with autistic children. New York: New York, 1970, 142p.23.Bosa C, Callias M. Autismo: breve revisão de diferentes abordagens. Psicol Reflex Crit 2000;13:167-77. http://dx.doi.org/10.1590/S0102-79722000000100017

O’Hare A. Autism spectrum disorder: diagnosis and management. Arch Dis Child Educ Pract Ed 2009;94:161-8. http://dx.doi.org/10.1136/adc.2008.150490

Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 1980;10:91-103. http://dx.doi.org/10.1007/BF02408436

Krug DA, Arick J, Almond P. Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. J Child Psychol Psychiatry 1980;21:221-9. http://dx.doi.org/10.1111/j.14697610.1980.tb01797.x

Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006;80:1-15. http://dx.doi.org/10.1189/jlb.1205707

Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology 1985; 35:866-74.

Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med 1988;318:1349-54. http://dx.doi.org/10.1056/NEJM198805263182102

Murakami JW, Courchesne E, Press GA, Yeung-Courchesne R, Hesselink JR. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol 1989;46:689-94.

Allen G, Courchesne E. Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism. Am J Psychiatry 2003;160:262-73. http://dx.doi.org/10.1176/appi.ajp.160.2.262

Gadia CA, Tuchman R, Rotta NT. Autism and pervasive developmental disorders. J Pediatr (Rio J) 2004;80:S83-94. http://dx.doi.org/10.2223/JPED.1172 http://dx.doi.org/10.2223/1172

Pardo CA, Vargas DL, Zimmerman AW. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 2005;17:485-95. http://dx.doi.org/10.1080/02646830500381930

Salgado-Pineda P, Delaveau P, Blin O, Nieoullon A. Dopaminergic contribution to the regulation of emotional perception. Clin Neuropharmacol 2005;28:228-37. http://dx.doi.org/10.1097/01.wnf.0000185824.57690.f0

Cook EH, Jr. Genetics of autism. Child Adolesc Psychiatr Clin N Am 2001;10:333-50.

Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D, Hallmayer J, et al. A genomic screen of autism: evidence for a multilocus etiology. Am J Hum Genet 1999;65:493-507. http://dx.doi.org/10.1086/302497

Cook EH, Jr., Courchesne R, Lord C, Cox NJ, Yan S, Lincoln A, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997;2:247-50. http://dx.doi.org/10.1038/sj.mp.4000266

Rapin I, Katzman R. Neurobiology of autism. Ann Neurol 1998;43:7-14. http://dx.doi.org/10.1002/ana.410430106

Newschaffer CJ, Fallin D, Lee NL. Heritable and nonheritable risk factors for autism spectrum disorders. Epidemiol Rev 2002;24:137-53. http://dx.doi.org/10.1093/epirev/mxf010

Cohen D, Pichard N, Tordjman S, Baumann C, Burglen L, Excoffier E, et al. Specific genetic disorders and autism: clinical contribution towards theiridentification. J Autism Dev Disord 2005;35:103-16. http://dx.doi.org/10.1007/s10803-004-1038-2

Deverman BE, Patterson PH. Cytokines and CNS development. Neuron 2009;64:61-78. http://dx.doi.org/10.1016/j.neuron.2009.09.002

Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 2010;23:103-10. http://dx.doi.org/10.1097/WCO.0b013e328336a01f

Wing L, Potter D. The epidemiology of autistic spectrum disorders: is the prevalence rising? Ment Retard Dev Disabil Res Rev 2002;8:151-61. http://dx.doi.org/10.1002/mrdd.10029

Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol 2005;161:916-28. http://dx.doi.org/10.1093/aje/kwi123

Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, et al. A clinicopathological study of autism. Brain 998;121(Pt 5):889-905. http://dx.doi.org/10.1093/brain/121.5.889

Guerin P, Lyon G, Barthelemy C, Sostak E, Chevrollier V, Garreau B, et al. Neuropathological study of a case of autistic syndrome with severe mental retardation. Dev Med Child Neurol 1996;38:203-11. http://dx.doi.org/10.1111/j.1469-8749.1996.tb15082.x

Warren RP, Margaretten NC, Pace NC, Foster A. Immune abnormalities in patients with autism. J Autism Dev Disord 1986;16:189-97. http://dx.doi.org/10.1007/BF01531729

van Gent T, Heijnen CJ, Treffers PD. Autism and the immune system. J Child Psychol Psychiatry 1997;38:337-49. http://dx.doi.org/10.1111/j.1469-7610.1997.tb01518.x

Dalton P, Deacon R, Blamire A, Pike M, McKinlay I, Stein J, et al. Maternal neuronal antibodies associated with autism and a language disorder. Ann Neurol 2003;53:533-7. http://dx.doi.org/10.1002/ana.10557

Zimmerman AW. The immune system. In: Bauman M, Kemper TL, editors. The neurobiology of autism. Baltimore: The Johns Hopkins University Press; 2005, p.371-86.

Dantzer R, Kelley KW. Autistic children: a neuroimmune perspective. Brain Behav Immun 2008;22:804-5. http://dx.doi.org/10.1016/j.bbi.2008.03.001

Stubbs EG, Crawford ML. Depressed lymphocyte responsiveness in autistic children. J Autism Child Schizophr 1977;7:49-55. http://dx.doi.org/10.1007/BF01531114

Gupta S, Aggarwal S, Rashanravan B, Lee T. Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998;85:106-9. http://dx.doi.org/10.1016/S0165-5728(98)00021-6

Singh VK, Warren R, Averett R, Ghaziuddin M. Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 1997;17:88-90. http://dx.doi.org/10.1016/S0887-8994(97)00045-3

Singh VK, Lin SX, Newell E, Nelson C. Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci 2002;9(4):359-64. http://dx.doi.org/10.1007/BF02256592

Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol 2002;129(1-2):168-77. http://dx.doi.org/10.1016/S01655728(02)00180-7

Jyonouchi H, Sun S, Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 2001;120(1-2):170-9. http://dx.doi.org/10.1016/S0165-5728(01)00421-0

Chess S, Fernandez P, Korn S. Behavioral consequences of congenital rubella. J Pediatr 1978;93:699-703. http://dx.doi.org/10.1016/S0022-3476(78)80921-4

Yamashita Y, Fujimoto C, Nakajima E, Isagai T, Matsuishi T. Possible association between congenital cytomegalovirus infection and autistic disorder. J Autism Dev Disord 2003;33:455-9. http://dx.doi.org/10.1023/A:1025023131029

Rosenberger PB. Editorial: Infectious disease and the immature brain. N Engl J Med 1975;293:39-40. http://dx.doi.org/10.1056/NEJM197507032930110

Sells CJ, Carpenter RL, Ray CG. Sequelae of central-nervous-system enterovirus infections. N Engl J Med 1975; 293:1-4. http://dx.doi.org/10.1056/NEJM197507032930101

Weinberg ED. Pregnancy-associated depression of cell-mediated immunity. Reviews of Infectious Diseases 1984;6:814-31. http://dx.doi.org/10.1093/clinids/6.6.814

Sargent IL. Maternal and fetal immune responses during pregnancy. Exp Clin Immunogenet 1993;10:85-102.

Munoz-Fernandez MA, Fresno M. The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Progress in Neurobiology 1998;56:307-40. http://dx.doi.org/10.1016/S0301-0082(98)00045-8

Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 2007;36:361-5. http://dx.doi.org/10.1016/j.pediatrneurol.2007.01.012

Sweeten TL, Posey DJ, McDougle CJ. High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry 2003;160:1691-3. http://dx.doi.org/10.1176/appi.ajp.160.9.1691

Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67-81. http://dx.doi.org/10.1002/ana.20315

Jansen LM, Gispen-de Wied CC, van der Gaag RJ, van Engeland H. Differentiation between autism and multiple complex developmental disorder in response to psychosocial stress. Neuropsychopharmacology 2003;28:582-90. http://dx.doi.org/10.1038/sj.npp.1300046

Tani P, Lindberg N, Matto V, Appelberg B, Nieminen-von Wendt T, von Wendt L, et al. Higher plasma ACTH levels in adults with Asperger syndrome. J Psychosom Res 2005;58:533-6. http://dx.doi.org/10.1016/j.jpsychores.2004.12.004

Boksa P. Effects of prenatal infection on brain development and behavior: A review of findings from animal models. Brain Behav Immun 2010;[in press]. http://dx.doi.org/10.1016/j.bbi.2010.03.005

Patterson PH. Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol 2002;12:115-8. http://dx.doi.org/10.1016/S0959-4388(02)00299-4

Meyer U, Yee BK, Feldon J. The neurodevelopmental impact of prenatal infections at different times of pregnancy: the earlier the worse? Neuroscientist 2007;13:241-56. http://dx.doi.org/10.1177/1073858406296401

Publicado
2012-03-31
Como Citar
Bernardi, M. M., Kirsten, T. B., & Trindade, M. O. (2012). Sobre o Autismo, Neuroinflamação e Modelos Animais para o Estudo de Autismo:. Revista Neurociências, 20(1), 117-127. https://doi.org/10.34024/rnc.2012.v20.8304
Seção
Artigos de Revisão