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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Melo, Roberto Laureano | |
| dc.date.accessioned | 2023-12-21T19:00:41Z | - |
| dc.date.available | 2023-12-21T19:00:41Z | - |
| dc.date.issued | 2017-10-21 | |
| dc.identifier.citation | MELO, Roberto Laureano. Avaliação psicobiológica em camundongos Swiss submetidos às manipulações farmacológicas do sistema serotonérgico durante o período neonatal. 2017. 68 f. Tese (Doutorado Multicêntrico em Ciências Fisiológicas) - Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ, 2017 . | por |
| dc.identifier.uri | https://rima.ufrrj.br/jspui/handle/20.500.14407/10301 | - |
| dc.description.abstract | A serotonina (5-HT) exerce um papel importante na embriogênese do sistema nervoso central de mamíferos, modulando a ontogenia de diversos sistemas neuronais, inclusive aqueles envolvidos com a regulação do humor e reatividade ao estresse. Nesse contexto, alterações na sinalização da 5-HT durante o início da vida podem comprometer a saúde mental e aumentar a susceptibilidade aos transtornos psiquiátricos. Dessa forma, o objetivo do nosso trabalho é avaliar se manipulações farmacológicas do sistema serotonérgico durante o período neonatal são capazes de alterar os parâmetros neurocomportamentais em prole de camundongos Swiss durante a fase adulta, bem como os mecanismos supostamente envolvidos. Para esse propósito, camundungas prenhas (n = 4 cada, e ~ 35g) foram divididas em seis grupos aleatoriamente. A prole obtida foi tratada com salina 0,9%, fluoxetina (FLU; 10mg/kg, s.c.), para-clorofenilalanina (p-CPA; 100mg/kg, s.c.), WAY 100135 (WAY; 1mg/kg, s.c.), 8-hidroxi-2-(di-n-propilamino) tetralina (DPAT; 1mg/kg, s.c.) do 5º ao 15º ou com d-fenfluramina (D-Fen; 3mg/kg, s.c.) do 5º ao 20º dia pós-natal. No 16º ou 21º dia pósnatal, parte da prole foi submetida à eutanásia, sendo o mesencéfalo e o hipocampo dissecados para análise da expressão dos seguintes genes: triptofano hidroxilase 2 (TPH2), transportador de 5-HT (SERT), receptor de 5-HT 1a (5-HT1a), fator neurotrófico derivado do cérebro (BDNF) e dos fatores de transcrição Pet1a e Lmx1b. O restante dos filhotes, ao completar 70 dias de vida, foi submetida a uma bateria de testes comportamentais composta dos seguintes protocolos: campo aberto, caixa claro-escuro, labirinto em cruz elevado e suspensão pela cauda. A análise estatística foi realizada pelo teste t de Student e as médias foram consideradas significativamente diferentes quando p < 0,05. Em relação aos achados transcricionais, foi verificado que aumento da neurotransmissão serotonérgica através do tratamento neonatal com D-Fen reduz a expressão mesencefálica de 5-HT1a (90%, p = 0,001), SERT (87%, p = 0,01), BDNF (70%, p = 0,001) e Pet1a (90%, p = 0,009), bem como a expressão de TPH2 (87%, p = 0,002) e BDNF (90%, p = 0.008) no hipocampo. O tratamento com Flu aumenta a expressão mesencefálica de TPH2 (98%, p = 0,004), mas diminui a expressão de TPH2 (93%, p < 0,001), 5HT1a (92%, p < 0.001), SERT (65%, p < 0,001), BDNF (80%, p = 0.001) e Lmx1b (97%, p = 0,001) no hipocampo. Em condições de depleção de 5-HT através do tratamento com p-CPA, há um aumento da expressão mesencefálica de 5-HT1a (35%, p = 0,02). Em relação às manipulações que envolvem o receptor 5-HT1a, a sua ativação através do tratamento com DPAT aumenta a expressão mesencefálica da TPH2 (66%, p = 0.03) e do próprio receptor 5-HT1a (54%, p = 0,01), mas reduz a expressão hipocampal de TPH2 (97%, p < 0,001), 5HT1a (28%, p = 0.03), SERT (64%, p = 0,003), BDNF (66%, p = 0,004) e Lmx1b (83%, p = 0,001). De maneira semelhante, o seu bloqueio através do tratamento com WAY aumenta a expressão mesencefálica de TPH2 (96%, p = 0,009), do próprio receptor 5-HT1a (78%, p < 0,001) e do SERT (95%, p = 0,002), mas reduz a expressão hipocampal de TPH2 (93%, p < 0.05), 5HT1a (47%, p = 0,01), SERT (58%, p = 0.01), BDNF (66%, p = 0,004) e Lmx1b (95%, p = 0,001). Quanto às avaliações comportamentais, no teste do campo aberto, nenhum dos tratamentos altera a atividade locomotora. Todavia tanto o tratamento com p-CPA quanto com WAY promovem redução da razão central (35%, p = 0,01 e 26%, p = 0,02, respectivamente). Já o tratamento com Flu aumenta o tempo de grooming (153%, p = 0,01). No teste da caixa claroVIII escuro, verificamos que há um aumento da latência e do tempo de permanência no lado claro nos tratamentos com D-Fen (87%, p = 0,01 e 21%, p =0,002) e Flu (764%, p = 0,01 e 108%, p = 0,008). No labirinto em cruz elevado, foi observado que o tratamento com DPAT aumenta o tempo de permanência e a porcentagem de entradas nos braços abertos (276%, p = 0,02 e 155%, p =0,03), ao passo que o WAY reduz (75%, p = 0,02 e 58%, p = 0,01). Já no teste da suspensão pela cauda, o tratamento com D-Fen, Flu ou DPAT reduz o tempo de imobilidade (98%, p < 0,001; 45%, p = 0,02 e 57%, p = 0,01, respectivamente), enquanto o tratamento com p-CPA ou WAY reduz a latência para o primeiro episódio de imobilidade (73%, p = 0,03 e 29%, p = 0,004, respectivamente). Dessa forma, conjecturamos que, através de mecanismos epigenéticos, manipulações farmacológicas que afetam a neurotransmissão serotonérgica durante o período neonatal promovem alterações neuroquímicas e hodológicas de sistemas cerebrais envolvidos com respostas afetivas, programando os comportamentos análogos à ansiedade e depressão na fase adulta. | por |
| dc.format | application/pdf | * |
| dc.language | por | por |
| dc.publisher | Universidade Federal Rural do Rio de Janeiro | por |
| dc.rights | Acesso Aberto | por |
| dc.subject | serotonina | por |
| dc.subject | desenvolvimento | por |
| dc.subject | ansiedade | por |
| dc.subject | depressão | por |
| dc.subject | serotonin | eng |
| dc.subject | development | eng |
| dc.subject | anxiety | eng |
| dc.subject | depression | eng |
| dc.title | Avaliação psicobiológica em camundongos swiss submetidos às manipulações farmacológicas do sistema serotonérgico durante o período neonatal | por |
| dc.title.alternative | Psychobiological evaluation in swiss mice underwent to neonatal pharmacological management of the serotonergic system | por |
| dc.type | Tese | por |
| dc.description.abstractOther | Serotonin (5-HT) plays an important role in the central nervous system embryogenesis of mammals, modulating the several neuronal systems ontogeny, including those involved in mood regulation and stress reactivity. In this context, changes in 5-HT signaling during early life can compromise the mental health and increase susceptibility to psychiatric disorders. Thus, the aim of our study is to assess whether neonatal pharmacological management of the serotonergic system are able to alter neurobehavioral parameters in Swiss mice offspring in adulthood, as well as the mechanisms supposedly involved. For this purpose, pregnant mice (n = 4 each, and ~ 35g) were randomly divided into six groups. The offspring obtained were treated with isotonic saline, fluoxetine (FLU, 10mg / kg, s.c.), para-chlorophenylalanine (p- CPA, 100mg / kg, s.c.), WAY 100135 (WAY, 1mg / kg, s.c.), 8-hydroxy-2-(di-propylamino)- tetraline (DPAT, 1mg / kg, s.c.) from 5th to 15th or with d-fenfluramine (D-fen, 3mg / kg, s.c.) from the 5th to the 20th postnatal day. On the 16th or 21st postnatal day, part of the offspring underwent to euthanasia, being the mesencephalon and hippocampus dissected for RNA analysis of the following genes: tryptophan hydroxylase 2 (TPH2), 5-HT transporter (SERT), 5-HT1a receptor (5-HT1a), brain derived neurotrophic factor (BDNF) and the transcription factors Pet1a and Lmx1b. The remaining offspring, at 70 days of age, underwent to a battery of behavioral tests composed by the following protocols: open field, dark light box, elevated plus maze and tail suspension tests. Statistical analysis were performed using T Student test and means were considered significantly different when p <0.05. Regarding the transcriptional findings, it was verified that increased serotonergic neurotransmission through neonatal treatment with D-Fen reduced mesencephalic expression of 5-HT1a (90%, p = 0.001), SERT (87%, p = 0.01), BDNF (70%, p = 0.001) and Pet1a (90%, p = 0.009), as well as TPH2 (87%, p = 0.002) and BDNF (90%, p = 0.008) expression in the hippocampus. Flu increases mesencephalic TPH2expression (98%, p = 0.004), however decreases the TPH2 (93%, p <0.001), 5HT1a (92%, p <0.001), SERT (65%, p <0.001), BDNF (80%, p = 0.001) and Lmx1b (97%, p = 0.001) expression in the hippocampus. Under 5-HT depletion conditions through p-CPA treatment, there is an increase in mesencephalic 5-HT1a expression (35%, p = 0.02). In relation to the manipulations involving the 5-HT1a receptor, its activation through DPAT treatment increases the mesencephalic expression of TPH2 (66%, p = 0.03) and 5-HT1a receptor itself (54%, p = 0.01 ), although it has reduced hippocampal expression of TPH2 (97%, p <0.001), 5HT1a (28%, p = 0.03), SERT (64%, p = 0.003), BDNF (66%, p = 0.004) and Lmx1b 83%, p = 0.001). Similarly, its blockade through WAY treatment increases the TPH2 (96%, p = 0.009), 5-HT1a receptor itself (78%, p <0.001) and SERT (95%, p = (P <0.05) mesencephalic expression, however reduced hippocampal expression of TPH2 (93%, p <0.05), 5HT1a (47%, p = 0.01), SERT (58%, p = 0.01), BDNF and Lmx1b (95%, p = 0.001). Regarding the behavioral evaluations, in the open field test, none of the treatments alter the locomotor activity. However, both p-CPA and WAY ones promoted reduction of the central ratio (35%, p = 0.01 and 26%, p = 0.02, respectively), whereas Flu increases grooming time (153%, p = 0.01). In the light-dark box test, there was an increase in latency and in light side time in treatments with D-Fen (87%, p = 0.01 and 21%, p = 0.002) and Flu (764 %, p = 0.01 and 108%, p = 0.008). In the elevated plus maze, it was verified that DPAT increases the time and the percentage of entries in the open arms (276%, p = 0.02 and 155%, p = 0.03), whereas X the WAY reduces (75%, p = 0.02 and 58%, p = 0.01). In tail suspension test, treatment with D-Fen, Flu or DPAT reduced the immobility time (98%, p <0.001, 45%, p = 0.02 and 57%, p = 0.01, respectively ), whereas p-CPA or WAY treatment reduced latency to immobility (73%, p = 0.03 and 29%, p = 0.004, respectively). Thus, we conjecture that, through epigenetic mechanisms, pharmacological management that affect serotonergic neurotransmission during the neonatal period promote neurochemical and hodological alterations of cerebral systems involved with affective responses, programming anxiety and depression like behaviors in adulthood | eng |
| dc.contributor.advisor1 | Côrtes, Wellington da Silva | |
| dc.contributor.advisor1ID | 86891600510 | por |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/1305510562756172 | por |
| dc.contributor.referee1 | Côrtes, Wellington da Silva | |
| dc.contributor.referee2 | Olivares, Emerson Lopes | |
| dc.contributor.referee3 | Giannocco, Gisele | |
| dc.contributor.referee4 | Reis, Luís Carlos | |
| dc.contributor.referee5 | Passos Júnior, Daniel Badauê | |
| dc.creator.ID | 12405535793 | por |
| dc.creator.Lattes | http://lattes.cnpq.br/1781979163325709 | por |
| dc.publisher.country | Brasil | por |
| dc.publisher.department | Instituto de Ciências Biológicas e da Saúde | por |
| dc.publisher.initials | UFRRJ | por |
| dc.publisher.program | Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas | por |
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