Polimorfismos corticais e subcorticais: implicações cognitivas e motoras
DOI:
https://doi.org/10.34024/rnc.2025.v33.19671Palavras-chave:
Genética, COMT, DRD2, BDNF, Funções cognitivas, Funções motorasResumo
Introdução. A aprendizagem de habilidades motoras depende de processos cognitivos, com a memória operacional (MO) desempenhando papel central nos estágios iniciais. Esse processo envolve planejamento cognitivo no córtex pré-frontal dorsolateral, planejamento motor em áreas motoras secundárias e execução na área motora primária. A MO inclui armazenamento e processamento de informações via ativação neuronal, com participação do córtex pré-frontal (CPF), núcleos da base e hipocampo. Polimorfismos genéticos, como Val158Met (COMT), TaqIA (DRD2/ANKK1) e Val66Met (BDNF), influenciam a MO e a aprendizagem motora. Método. Este estudo revisou pesquisas sobre esses polimorfismos e suas implicações nas funções cognitivas e motoras, utilizando bases como PubMed, Scopus e Web of Science. Resultados. Enquanto alguns estudos identificaram associações entre genótipos e desempenho cognitivo/motor, outros foram inconclusivos, sugerindo que fatores genéticos e ambientais adicionais podem modular esses efeitos. Estudos que analisaram interações entre polimorfismos revelaram efeitos complexos, especialmente entre COMT e DRD2/ANKK1, dependendo do equilíbrio entre neurotransmissores e receptores em diferentes regiões encefálicas. Interações mais intensas foram observadas em alelos de alto desempenho. Compreender esses polimorfismos é essencial para esclarecer o funcionamento cerebral e suas interações, com impacto nas funções cognitivas e motoras, cruciais para o cotidiano. Conclusão. Estudos futuros devem considerar variáveis adicionais, como o tipo de tarefa e o tamanho da amostra, para aprofundar o conhecimento sobre os mecanismos das funções cognitivas e motoras.
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Referências
Anguera JA, Reuter-Lorenz PA, Willingham DT, Seidler RD. Contributions of spatial working memory to visuomotor learning. J Cogn Neurosci 2010;22:1917-30. https://doi.org/10.1162/jocn.2009.21351
Bo J, Seidler RD. Visuospatial working memory capacity predicts the organization of acquired explicit motor sequences. J Neurophysiol 2009;101:3116-25. https://doi.org/10.1152/jn.00006.2009
Seidler RD, Bo J, Anguera JA. Neurocognitive contributions to motor skill learning: the role of working memory. J Motor Behav 2012;44:445-53. https://doi.org/10.1080/00222895.2012.672348
Diamond A. Executive functions. Ann Rev Psychol 2013;64:135-68. https://doi.org/10.1146/annurev-psych-113011-143750
Frank MJ, Loughry B, O'Reilly RC. Interactions between frontal cortex and basal ganglia in working memory: a computational model. Cogn Affec Behav Neurosci 2001;1:137-60. https://doi.org/10.3758/cabn.1.2.137
Stelzel C, Basten U, Montag C, Reuter M, Fiebach CJ. Effects of dopamine-related gene-gene interactions on working memory component processes. Eur J Neurosci 2009;29:1056-63. https://doi.org/10.1111/j.1460-9568.2009.06647.x
Berryhill ME, Wiener M, Stephens JA, Lohoff FW, Coslett HB. COMT and ANKK1-Taq-Ia genetic polymorphisms influence visual working memory. PloS one 2013;8:e55862. https://doi.org/10.1371/journal.pone.0055862
Baier B, Karnath HO, Dieterich M, Birklein F, Heinze C, Muller NG. Keeping memory clear and stable--the contribution of human basal ganglia and prefrontal cortex to working memory. J Neurosci 2010;30:9788-92. https://doi.org/10.1523/JNEUROSCI.1513-10.2010
Cools R. Role of dopamine in the motivational and cognitive control of behavior. Neurosci Review J Neurobiol Neurol Psychiatr 2008;14:381-95. https://doi.org/10.1177/1073858408317009
Ferenhof HA, Fernandes RF. Desmistificando a revisão de literatura como base para redação científica: método SFF. Rev ACB 2016;21:550-63. https://revista.acbsc.org.br/racb/article/view/1194
Rother ET. Revisão sistemática X revisão narrativa. Acta Paul 2007;20:editotial. https://doi.org/10.1590/S0103-21002007000200001
Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Gen 2004;75:807-21. https://doi.org/10.1086/425589
Lage GM, Miranda DM, Romano-Silva MA, Campos SB, Albuquerque MR, Correa H, et al. Association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and manual aiming control in healthy subjects. PloS one 2014;9:e99698. https://doi.org/10.1371/journal.pone.0099698
Bilder RM, Volavka J, Lachman HM, Grace AA. The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacol 2004;29:1943-61. https://doi.org/10.1038/sj.npp.1300542
Tunbridge EM, Harrison PJ, Weinberger DR. Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol Psychiatr 2006;60:141-51. https://doi.org/10.1016/j.biopsych.2005.10.024
Rosa EC, Dickinson D, Apud J, Weinberger DR, Elvevag B. COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination. Behav Brain Funct 2010;6:53. https://doi.org/10.1186/1744-9081-6-53
Barnett JH, Scoriels L, Munafo MR. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatr 2008;64:137-44. https://doi.org/10.1016/j.biopsych.2008.01.005
Garcia-Garcia M, Barcelo F, Clemente IC, Escera C. COMT and ANKK1 gene-gene interaction modulates contextual updating of mental representations. NeuroImage 2011;56:1641-7. https://doi.org/10.1016/j.neuroimage.2011.02.053
Nogueira N, Fernandes LA, Ferreira BP, Batista MTS, Alves KCR, Parma JO. Association Between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Manual Performance Asymmetries. Percep Motor Skills 2019;126:349-65. https://doi.org/10.1177/0031512519834738
Nogueira N, Miranda DM, Albuquerque MR, Ferreira BP, Batista MTS, Parma JO, et al. Motor learning and COMT Val158met polymorphism: Analyses of oculomotor behavior and corticocortical communication. Neurobiol Learn Mem 2020;168:107157. https://doi.org/10.1016/j.nlm.2020.107157
Savitz J, Solms M, Ramesar R. The molecular genetics of cognition: dopamine, COMT and BDNF. Gen Brain Behav 2006;5:311-28. https://doi.org/10.1111/j.1601-183X.2005.00163.x
Ariza M, Garolera M, Jurado MA, Garcia-Garcia I, Hernan I, Sanchez-Garre C, et al. Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their interaction with obesity. PloS one 2012;7:e41482. https://doi.org/10.1371/journal.pone.0041482
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 1986;9:357-81. https://doi.org/10.1146/annurev.ne.09.030186.002041
Cools R. Dopaminergic control of the striatum for high-level cognition. Curr Opin Neurobiol 2011;21:402-7. https://doi.org/10.1016/j.conb.2011.04.002
Noble EP. Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review. Eur Psychiatr 2000;15:79-89. https://doi.org/10.1016/s0924-9338(00)00208-x
Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat 2004;23:540-5. https://doi.org/10.1002/humu.20039
Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, et al. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 1997;7:479-84. https://doi.org/10.1097/00008571-199712000-00006
Baetu I, Burns NR, Urry K, Barbante GG, Pitcher JB. Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans. Neurobiol Learn Mem 2015;125:176-88. https://doi.org/10.1016/j.nlm.2015.09.009
Noohi F, Boyden NB, Kwak Y, Humfleet J, Burke DT, Muller ML, et al. Association of COMT val158met and DRD2 G>T genetic polymorphisms with individual differences in motor learning and performance in female young adults. J Neurophysiol 2014;111:628-40. https://doi.org/10.1152/jn.00457.2013
Wishart HA, Roth RM, Saykin AJ, Rhodes CH, Tsongalis GJ, Pattin KA, et al. COMT Val158Met Genotype and Individual Differences in Executive Function in Healthy Adults. J Inter Neuropsychol Soc 2011;17:174-80. https://doi.org/10.1017/S1355617710001402
Noohi F, Boyden NB, Kwak Y, Humfleet J, Muller ML, Bohnen NI, et al. Interactive effects of age and multi-gene profile on motor learning and sensorimotor adaptation. Neuropsychol 2016;84:222-34. https://doi.org/10.1016/j.neuropsychologia.2016.02.021
Apolinário-Souza T. Processos de formação de memória envolvidos na organização da prática (Tese). Belo Horizonte: Escola de Educação Física Fisioterapia e Terapia Ocupacional, Universidade Federal de Minas Gerais; 2018. https://repositorio.ufmg.br/bitstream/1843/30670/1/Versao_final.pdf
Palasz E, Wysocka A, Gasiorowska A, Chalimoniuk M, Niewiadomski W, Niewiadomska G. BDNF as a Promising Therapeutic Agent in Parkinson's Disease. Inter J Mol Sci 2020;21:1-23. https://doi.org/10.3390/ijms21031170
Lemos Jr. JR, Alves CR, Souza SB, Marsiglia JD, Silva MS, Pereira AC, et al. Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism. Physiol Genom 2016;48:116-23. https://doi.org/10.1152/physiolgenomics.00086.2015
Nagel IE, Chicherio C, Li SC, von Oertzen T, Sander T, Villringer A, et al. Human aging magnifies genetic effects on executive functioning and working memory. Front Hum Neurosci 2008;2:1. https://doi.org/10.3389/neuro.09.001.2008
Bertolino A, Rubino V, Sambataro F, Blasi G, Latorre V, Fazio L, et al. Prefrontal-hippocampal coupling during memory processing is modulated by COMT val158met genotype. Biol Psychiatr 2006;60:1250-8. https://doi.org/10.1016/j.biopsych.2006.03.078
Rybakowski JK, Borkowska A, Czerski PM, Skibinska M, Hauser J. Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients. Bipolar Dis 2003;5:468-72. https://doi.org/10.1046/j.1399-5618.2003.00071.x
Goldberg TE, Weinberger DR. Genes and the parsing of cognitive processes. Trends Cogn Sci 2004;8:325-35. https://doi.org/10.1016/j.tics.2004.05.011
Noble EP. The DRD2 gene in psychiatric and neurological disorders and its phenotypes. Pharmacogenomics 2000;1:309-33. https://doi.org/10.1517/14622416.1.3.309
Witte AV, Floel A. Effects of COMT polymorphisms on brain function and behavior in health and disease. Brain Res Bull 2012;88:418-28. https://doi.org/10.1016/j.brainresbull.2011.11.012
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Copyright (c) 2025 Nathálya Gardênia de Holanda Marinho Nogueira, Bárbara de Paula Ferreira, Sara Edith Souza de Assis Leão, Viviane Lima Gonçalves, Ana Beatriz Borges Duarte, Guilherme Menezes Lage
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Aprovado 2025-04-09
Publicado 2025-04-16
