Atividade serotoninérgica perinatal: um fator decisivo para o controle da ingestão alimentar
Palavras-chave:
Ingestão de alimentos, Desnutrição, Serotonina, Inibidores da captação de serotoninaResumo
O sistema serotoninérgico apresenta funções no controle de eventos biológicos fundamentais para o desenvolvimento adequado do sistema nervoso. A serotonina e o transportador de serotonina são indispensáveispara esta função de controle. A disponibilidade destes componentes é precisamente regulada durante o período de desenvolvimento, e podem sofrer interferências provindas do ambiente alterando sua ação sobre o sistema nervoso. A desnutrição, a inibição da recaptação da serotonina a partir de fármacos e mudanças na expressão de gênica do transportador de serotonina na gestação e lactação podem induzir o aumento de serotonina alterando sua ação anorexígena. As respostas fisiológicas desempenhadas pela serotonina no controle da ingestão exibem uma resistência quando requisitadas por estímulos ou estresses agudos, demonstrando que os animais ou indivíduos desenvolvem adaptações de acordo com as agressões ambientais sofridas no período de desenvolvimento. Patologias como, ansiedade e obesidade, parecem estar associadas à resposta do organismo a um estresse ou estímulo, necessitando de uma maior ação do sistema serotoninérgico. Estes achados demonstram a importância do conteúdo da serotonina no período perinatal ao desenvolvimento de aspectos moleculares e morfológicos do controle da ingestão alimentar, e sua função determinante para a compreensão das possíveis influências ambientais causadoras de patologias na vida adulta.
Referências
Lidov H, Molliver M. An immunohistochemical study of serotonin neuron development in the rat: Ascending pathways and terminal fields. Brain Res Bull. 1982;8(4):389-430. https://doi.org/10.1016/0361-9230(82)90077-6
Manjarrez G, Chagoya G, Hernández R J. Early nutritional changes modify the kinetics and phosphorylation capacity of tryptophan-5-hydroxylase. Int J Dev Neurosci. 1994;12(8):695-702. https://doi.org/10.1016/0736-5748(94)90 049-3
Galindo LCM, Barros MLD, Pinheiro IL, Santana RVC, Matos RJB, Leandro CG, et al. Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats. Int J Dev Neurosci. 2015;46:76-81. https://doi.org/10.1016/j.ijdevneu.2015.07.004
Miranda R, Vetter S, Genro J, Campagnolo P, Mattevi V, Vitolo M, et al. SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children. Clin Biochem. 2015;48(18):1277-82. https://doi.org/10.1016/j.clinbiochem.2015.07.003
Wells J. Adaptive variability in the duration of critical windows of plasticity: Implications for the programming of obesity. Evol Med Public Health. 2014;2014(1):109-21. https://doi.org/10.1093/emph/eou019
Ravelli G, Stein Z, Susser M. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976;295(7):349-53. https://doi.org/10.1056/NEJM197608122950701
Neel JV. Diabetes Mellitus: A “thrifty” genotype rendered detrimental by “Progress”? Am J Hum Genet. 1962;14(4):353-62.8. Dobbing J. Undernutrition and the developing brain: The relevance of animal models to the human problem. Am J Dis Child. 1970;120(5):411.
Morgane P, Miller M, Kemper T, Stern W, Forbes W, Hall R, et al. The effects of protein malnutrition on the developing central nervous system in the rat. Neuro Sci Bio Behav Rev. 1978;2(3):137-230. https://doi.org/10.1016/0149-7634(78)90059-3
Hales C, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60(1):5-20. https://doi.org/10.1093/bmb/60.1.5
Gluckman P, Hanson M, Low F. The role of developmental plasticity and epigenetics in human health. Birth Defects Res C Embryo Today. 2011;93(1):12-18. https://doi.org/10.1002/bdrc.20198
Skinner MK, Manikkam M, Guerrero-Bosagna C. Epigenetic transgenerational actions of endocrine disruptors. Reprod Toxicol. 2011;31(5727):337-43. https://doi.org/10.1016/j.reprotox.2010.10.012
Whitaker-Azmitia PM, Druse M, Walker P, Lauder JM. Serotonin as a developmental signal. Behav Brain Res. 1996;(73):19-29.
Sundstrom E, Kolare S, Souverbie F, Samuelsson EB, Pschera H, Lunell NO, et al. Neurochemical differentiation of human bulbospinal monoaminergic neurons during the first trimester. Brain Res Dev Brain Res. 1993;(75):1-12
Gaspar, P, Cases O, Maroteaux, l. The developmental role of serotonin: News from mouse molecular genetics. Nat Rev Neuro Sci. 2003;4(12):1002-12. https://doi.org/10.1038/nrn1256
Walther D, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, et al. Synthesis of Serotonin by a Second Tryptophan Hydroxylase Isoform. Science. 2003;299(5603):76. https://doi.org/10.1126/science.1078197
Chugani DC, Muzik O, Behen M, Rothermel R, Janisse JJ, Lee J, et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol. 1999;45(3):287-95.
Morton G, Cummings D, Baskin D, Barsh G, Schwartz M. Central nervous system control of food intake and body weight. Nature. 2006;443(7109):289-95. https://doi.org/10.1038/nature05026
Riccio O, Jacobshagen M, Golding B, Vutskits L, Jabaudon D, Hornung, et al. Excess of serotonin affects neocortical pyramidal neuron migration. Transl Psychiatry. 2011;1(10):e47. https://doi.org/10.1038/tp.2011.49
Azmitia EC. Evolution of serotonin: Sunlight to suicide. In: Muller CP, Jacobs BL, editors. London: Handbook of the behavioral neurobiology of serotonin. London: Academic Press; 2010. p.3-22.
Sablin S, Yankovskaya V, Bernard S, Cronin C, Singer T. Isolation and characterization of an evolutionary precursor of human monoamine oxidases A and B. Eur J Biochem. 1998;253(1):270-9.
Sghendo L, Mifsud J. Understanding the molecular pharmacology of the serotonergic system: Using fluoxetine as a model. J Pharm Pharmacol. 2012;64(3):317-25. https://doi.org/10.1111/j.2042-7158.2011.01384.x
Bonnin A, Levitt P. Fetal, maternal and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience. 2011;197:1-7. https://doi.org/10.1016/j.neuroscience.2011.10.005
Huether G, Thornke F, Adler L. Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring. Dev Brain Res. 1992;68(2):175-81.
Wallace JA, Lauder JM. Development of the serotonergic system in the rat embryo: An immunocytochemical study. Brain Res Bull. 1983;10(4):459-79.
Sodhi MS, Sanders-Bush E. Serotonin and brain development. Int Rev Neurobiol. 2004;(59):111-74. https://doi.org/10.1016/S0074-7742(04)59006-2
De Vitry F, Hamon M, Catelon J, Dubois M, Thibault J. Serotonin initiates and auto-amplifies its own synthesis during mouse central nervous system development. Proc Natl Acad Sci. 1986;(22):8629-33.
Hensler JG. Serotonin. In: Siegel GJ, Albers RW, Scott B, Price DD, editors. Basic neurochemistry: Molecular, cellular and medical aspects. San Diego: Academic Press; 2006. p.227-48.
Schwartz GJ. Integrative capacity of the caudal brainstem in the control of food intake. Philos Trans R Soc Lond B Biol Sci. 2006;361(1471):1275-80. https://doi.org/10.1098/rstb.2006.1862
Jiang C, Fogel R, Zhang X. Lateral hypothalamus modulates gut-sensitive neurons in the dorsal vagal complex. Brain Res. 2003;980(1):31-47. https://doi.org/10.1016/S0006-8993(3)02844-0
Zhang X, Cui J, Tan Z, Jiang C, Fogel R. The central nucleus of the amygdala modulates gutrelated neurons in the dorsal vagal complex in rats. J Physiol. 2003;553(Pt.3):1005-18. https://doi.org/10.1113/jphysiol.2003.045906
Rinaman L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res. 2010;1350:18-34. https://doi.org/10.1016/j.brainres.2010.03.059
Halford JC, Harrold JA, Lawton CL, Blundell JE. Serotonin (5-HT) drugs: Effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 2005;6(2):201-13. https://doi.org/10.2174/1389450053174550
Heisler L, Jobst E, Sutton G, Zhou L, Borok E, Thornton-Jones Z, et al. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron. 2006;51(2):239-49. https://doi.org/10.1016/j.neuron.2006.06.004
Bendotti C, Samanin R. 8-Hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) elicits eating in free-feeding rats by acting on central serotonin neurons. Eur J Pharmacol. 1986;121(1):147-50.
Weiss GF, Rogacki N, Fueg A, Buchen D, Leibowitz SF. Impact of hypothalamic d-norfenfluramine and peripheral d-fenfluramine injection on macronutrient intake in the rat. Brain Res Bull. 1990;25(6):849-59.
Lopes de Souza S, Orozco-Solis R, Grit I, Manhães de Castro R, Bolaños-Jiménez F. Perinatal protein restriction reduces the inhibitory action of serotonin on food intake. Eur J Neurosci. 2008;27(6):1400-8. https://doi.org/10.1111/j.1460-9568.2008.06105.x
Lira L, Almeida L, da Silva A, Cavalcante T, de Melo D, de Souza J, et al. Perinatal undernutrition increases meal size and neuronal activation of the nucleus of the solitary tract in response to feeding stimulation in adult rats. Int J Dev Neurosci. 2014;38:23-9. https://doi.org/10.1016/j.ijdevneu.2014.07.007
Ferraz-Pereira K, da Silva Aragão R, Verdier D, Toscano A, Lacerda D, Manhães-de-Castro R, et al. Neonatal low-protein diet reduces the masticatory efficiency in rats. Br J Nutr. 2015;114(9):1515-30.
Carvalho-Santos J, Queirós-Santos A, Morais GL, Santana LH, Brito MG, Araújo RCS, et al. Efeito do tratamento com triptofano sobre parâmetros do comportamento alimentar em ratos adultos submetidos à desnutrição neonatal. Rev Nutr. 2010;23(4):503-11. https://doi.org/10.1590/S1415-52732010000400001
Resnick O, Miller M, Forbes W, Hall R, Kemper T, Bronzino J, et al. Developmental protein malnutrition: Influences on the central nervous system of the rat. Neurosci Biobehav Rev. 1979;3(4):233-46.
Mathews T, Fedele D, Coppelli F, Avila A, Murphy D, Andrews A. Gene dose-dependent alterations in extraneuronal serotonin but not dopamine in mice with reduced serotonin transporter expression. J Neurosci Methods. 2004;140(1-2):169-81. https://doi.org/10.1016/j.jneumeth.2004.05.017
Holmes A, Murphy DL, Crawley JN. Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology. 2002;27(6):914-23. https://doi.org/10.1016/S0893-133X(02)00374-3
Jennings K. Increased expression of the 5-ht transporter confers a low- anxiety phenotype linked to decreased 5-ht transmission. J Neurosci. 2006;26(35):8955-64. https://doi.org/10.1523/JNEUROSCI.5356-05.2006
Pringle A, Jennings K, Line S, Bannerman D, Higgs S, Sharp T. Mice overexpressing the 5-hydroxytryptamine transporter show no alterations in feeding behaviour and increased non-feeding responses to fenfluramine. Psychopharmacology. 2008;200(2):291-300. https://doi.org/10.1007/s00213-008-1206-8
Silva CM, Gonçalves L, Manhaes-de-Castro R, Nogueira MI. Postnatal fluoxetine treatment affects the development of serotonergic neurons in rats. Neurosci Lett. 2010;483(3):179-83. https://doi.org/10.1016/j.neulet.2010.08.003
Deiró T, Manhães-de-Castro R, Cabral-Filho J, Souza S, Freitas-Silva S, Ferreira L, et al. Neonatal administration of citalopram delays somatic maturation in rats. Braz J Med Biol Res. 2004;37(10):1503-9. https://doi.org/10.1590/S0100-879X2004001000009
Grove KL, Smith MS. Ontogeny of the hypothalamic neuropeptide Y system. Physiol Behav. 2003;79(1):47-63. https://doi.org/10.1016/S0031-9384(03)00104-5
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Copyright (c) 2023 Isabeli Lins PINHEIRO, Bárbara Juacy Rodrigues Costa DE SANTANA, Lígia Cristina Monteiro GALINDO, Raul MANHÃES DE CASTRO, Sandra Lopes de SOUSA
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