Estudo dos efeitos da exposição de toxina botulínica "A" durante a gestação no comportamento materno de ratas e possíveis implicações comportamentais na prole infantil
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Tipo
TCC
Data de publicação
2023-12
Periódico
Citações (Scopus)
Autores
Silva, Mayara Rosseti
Orientador
Camargo, Esther Lopes Ricci Adari
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Resumo
A toxina botulínica A (BoNtA) é um dos sete sorotipos produzidos pelo bacilo Clostridium botulinum que se tornou amplamente utilizado na estética e terapia humana após se mostrar eficaz no tratamento de diversos distúrbios musculoesqueléticos e neurológicos. Seu mecanismo de ação ocorre através do bloqueio de exocitose de acetilcolina nas placas terminais nervosas colinérgicas, sendo esse o principal neurotransmissor na junção neuromuscular. No entanto, há uma lacuna no que tange ao seu uso durante períodos críticos de desenvolvimento, como a gestação, lactação e infância. Sendo assim, seu uso durante a gravidez é classificado no nível C de risco pela FDA e pela ANVISA, justificando que o seu uso durante esse período só deve ocorrer se o benefício para a mãe justificar o risco para o feto. A fim de investigar possíveis efeitos da BoNtA durante a gestação, o presente trabalho se propôs a avaliar o desempenho reprodutivo e comportamento materno de ratas gestantes expostas à essa substância e possíveis implicações comportamentais na prole infantil. Para isso foram utilizadas 32 ratas divididas em 1 grupo controle e 3 grupos experimentais (4, 8 e 16U/Kg) que receberam dose única de BoNtA ou solução salina no DG (dia de gestação) 5. Para avaliação do comportamento materno antes do nascimento dos filhotes, no DG20 foi realizado o nest building test. Em seguida, no dia de lactação (DL) 2 foi analisado o desempenho reprodutivo das ratas e no DL5 foi realizado o teste do comportamento materno para avaliação desse parâmetro após o nascimento da prole. Para os testes com a prole infantil, foi realizado o marble burying test no dia pós nascimento (DPN) 24 para avaliação do comportamento tipo-ansioso, e o teste do comportamento de brincar de luta (play Fighting) no DPN30 para avaliação da sociabilidade da prole durante a infância. Todas as análises ocorreram com ANOVA de uma via através do software GraphPad Prism 8®. Os resultados não apresentaram diferenças significativas entre o grupo controle e os grupos experimentais. Sendo assim, a aplicação de BoNtA durante a gestação não apresentou efeitos em ratas, mas ainda é necessário realizar novos trabalhos para obtenção de dados conclusivos.
Botulinum toxin type A (BoNtA) is one of the seven serotypes produced by the bacterium Clostridium botulinum. It has become widely used in aesthetics and human therapy after proving effective in the treatment of various musculoskeletal and neurological disorders. Its mechanism of action involves blocking the exocytosis of acetylcholine at cholinergic nerve terminal plates, which is the primary neurotransmitter at the neuromuscular junction. However, there is a gap in its use during critical developmental periods, such as pregnancy, lactation, and childhood. Consequently, its use during pregnancy is classified as level C risk by the FDA and ANVISA, justifying that it should only occur if the benefit to the mother outweighs the risk to the fetus. In order to investigate potential effects of BoNtA during pregnancy, this study aimed to assess the reproductive performance and maternal behavior of pregnant rats exposed to this substance and possible behavioral implications in the offspring. For this purpose, 32 female rats were divided into 1 control group and 3 experimental groups (4, 8, and 16U/kg) that received a single dose of BoNT-A or saline solution on gestation day 5. To evaluate maternal behavior before the birth of the offspring, the nest building test was conducted on gestation day 20. Subsequently, on lactation day 2, the reproductive performance of the rats was analyzed, and on lactation day 5, the maternal behavior test was conducted to assess this parameter after the birth of the offspring. For tests with the offspring, the marble burying test was performed on postnatal day 24 to evaluate anxious-type behavior, and the play-fighting behavior test on postnatal day 30 to assess offspring sociability during childhood. All analyses were conducted using one-way ANOVA through GraphPad Prism 8® software. The results showed no significant differences between the control group and the experimental groups. Therefore, BoNT-A application during pregnancy did not show effects in rats, but further studies are still necessary to obtain conclusive data.
Botulinum toxin type A (BoNtA) is one of the seven serotypes produced by the bacterium Clostridium botulinum. It has become widely used in aesthetics and human therapy after proving effective in the treatment of various musculoskeletal and neurological disorders. Its mechanism of action involves blocking the exocytosis of acetylcholine at cholinergic nerve terminal plates, which is the primary neurotransmitter at the neuromuscular junction. However, there is a gap in its use during critical developmental periods, such as pregnancy, lactation, and childhood. Consequently, its use during pregnancy is classified as level C risk by the FDA and ANVISA, justifying that it should only occur if the benefit to the mother outweighs the risk to the fetus. In order to investigate potential effects of BoNtA during pregnancy, this study aimed to assess the reproductive performance and maternal behavior of pregnant rats exposed to this substance and possible behavioral implications in the offspring. For this purpose, 32 female rats were divided into 1 control group and 3 experimental groups (4, 8, and 16U/kg) that received a single dose of BoNT-A or saline solution on gestation day 5. To evaluate maternal behavior before the birth of the offspring, the nest building test was conducted on gestation day 20. Subsequently, on lactation day 2, the reproductive performance of the rats was analyzed, and on lactation day 5, the maternal behavior test was conducted to assess this parameter after the birth of the offspring. For tests with the offspring, the marble burying test was performed on postnatal day 24 to evaluate anxious-type behavior, and the play-fighting behavior test on postnatal day 30 to assess offspring sociability during childhood. All analyses were conducted using one-way ANOVA through GraphPad Prism 8® software. The results showed no significant differences between the control group and the experimental groups. Therefore, BoNT-A application during pregnancy did not show effects in rats, but further studies are still necessary to obtain conclusive data.
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comportamneto animal , toxicidade , toxina botulínica , acetilcolina , cuidado materno , animal behavior , maternal care , toxicity , botulinum toxin , acetylcholine