Análise da influência de probióticos no sistema serotoninérgico e neurotrofina BDNF no hipocampo e córtex pré-frontal de ratos nutridos e desnutridos
Data
2022-07-29
Autores
Fonseca, Samantha Timoteo Oliveira da 
Orientadores
Mendes-da-Silva, Cristiano
Tipo
Dissertação de mestrado
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Introdução: A comunicação bidirecional entre a microbiota intestinal, o sistema serotoninérgico e neurotrofina BDNF (Brain-derived neurotrophic factor) no córtex pré-frontal e hipocampo pode ser modulada pela terapia probiótica, determinando efeitos comportamentais e cognitivos diante de diferentes eventos como antibioticoterapia, estresse e dieta hiperlipídica. Todavia, não são descritos efeitos na desnutrição por déficit calórico-proteico. Objetivo: Avaliar os efeitos dos probióticos no sistema serotoninérgico e a neurotrofina BDNF no córtex pré-frontal e hipocampo de ratos nutridos e desnutridos. Métodos: Foram estudados 38 ratos isogênicos, Lewis, com 7 a 8 semanas, distribuídos em quatro grupos: nutrido placebo (n=9), desnutrido placebo (n=9), nutrido probiótico (n=10) e desnutrido probiótico (n=10). Os animais desnutridos ingeriram 30-40% menos alimento que o consumido pelos nutridos e o probiótico consistia no composto de Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis administrado diariamente, via gavagem. A suplementação iniciou após 10 dias de desnutrição e persistiu junto à restrição por mais 15 dias. Após os 25 dias de experimento, os animais foram eutanasiados, foram extraídos os hipocampos e córtex pré-frontal para análise por immunoblotting dos receptores serotoninérgicos 5-HT1a e 5-HT2c, da enzima de síntese de serotonina TPH2 (triptofano hidroxilase 2) e da neurotrofina BDNF. Para análise estatística utilizou-se GEE (Generalized Estimating Equation) e GzLM (Generalized Linear Model), assumindo um nível de significância p<0,05. Resultados: A administração probiótica aumentou as expressões proteicas do receptor 5-HT2c no córtex pré-frontal dos nutridos e desnutridos, da enzima TPH2 no córtex pré-frontal dos nutridos e no hipocampo dos desnutridos e normalizou os níveis de pró-BDNF em ambos tecidos e condições nutricionais. Conclusões: A suplementação de Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis melhorou a atividade do sistema serotoninérgico no hipocampo e córtex pré-frontal durante a desnutrição.
Introduction: The bidirectional communication between the intestinal microbiota, the serotonergic system and BDNF (Brain-derived neurotrophic factor) neurotrophin in the prefrontal cortex and hippocampus can be modulated by probiotic therapy, determining behavioral and cognitive effects in the face of different events such as antibiotic therapy, stress and high-fat diet. However, no effects on malnutrition due to protein-calorie deficit are described. Objective: To evaluate the effects of probiotics on the serotonergic system and the neurotrophin BDNF in the prefrontal cortex and hippocampus of nourished and malnourished rats. Methods: We studied 38 isogenic Lewis rats, aged 7 to 8 weeks, divided into four groups: placebo nourished (n=9), placebo malnourished (n=9), probiotic nourished (n=10) and probiotic malnourished (n= 10). The malnourished animals ingested 30-40% less food than that consumed by the nourished and the probiotic consisted of the compound of Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis administered daily via gavage. Supplementation started after 10 days of malnutrition and persisted with restriction for another 15 days. After 25 days of experiment, the animals were euthanized, the hippocampi and prefrontal cortex were extracted for immunoblotting analysis of the serotonergic receptors 5- HT1a and 5-HT2c, the serotonin synthesis enzyme TPH2 (tryptophan hydroxylase 2) and the BDNF neurotrophin. For statistical analysis, GEE (Generalized estimating equation) and GzLM (Generalized linear model) were used, assuming a significance level of p<0.05. Results: Probiotic administration increased the protein expressions of the 5-HT2c receptor in the prefrontal cortex of the nourished and malnourished, of the TPH2 enzyme in the prefrontal cortex of the nourished and in the hippocampus of the malnourished and normalized pro-BDNF levels in both tissue and nutritional conditions. Conclusions: Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis supplementation improved the activity of the serotonergic system in the hippocampus and prefrontal cortex during undernutrition.
Introduction: The bidirectional communication between the intestinal microbiota, the serotonergic system and BDNF (Brain-derived neurotrophic factor) neurotrophin in the prefrontal cortex and hippocampus can be modulated by probiotic therapy, determining behavioral and cognitive effects in the face of different events such as antibiotic therapy, stress and high-fat diet. However, no effects on malnutrition due to protein-calorie deficit are described. Objective: To evaluate the effects of probiotics on the serotonergic system and the neurotrophin BDNF in the prefrontal cortex and hippocampus of nourished and malnourished rats. Methods: We studied 38 isogenic Lewis rats, aged 7 to 8 weeks, divided into four groups: placebo nourished (n=9), placebo malnourished (n=9), probiotic nourished (n=10) and probiotic malnourished (n= 10). The malnourished animals ingested 30-40% less food than that consumed by the nourished and the probiotic consisted of the compound of Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis administered daily via gavage. Supplementation started after 10 days of malnutrition and persisted with restriction for another 15 days. After 25 days of experiment, the animals were euthanized, the hippocampi and prefrontal cortex were extracted for immunoblotting analysis of the serotonergic receptors 5- HT1a and 5-HT2c, the serotonin synthesis enzyme TPH2 (tryptophan hydroxylase 2) and the BDNF neurotrophin. For statistical analysis, GEE (Generalized estimating equation) and GzLM (Generalized linear model) were used, assuming a significance level of p<0.05. Results: Probiotic administration increased the protein expressions of the 5-HT2c receptor in the prefrontal cortex of the nourished and malnourished, of the TPH2 enzyme in the prefrontal cortex of the nourished and in the hippocampus of the malnourished and normalized pro-BDNF levels in both tissue and nutritional conditions. Conclusions: Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium lactis supplementation improved the activity of the serotonergic system in the hippocampus and prefrontal cortex during undernutrition.
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Citação
FONSECA, Samantha Timoteo Oliveira da. Análise da influência de probióticos no sistema serotoninérgico e neurotrofina BDNF no hipocampo e córtex pré-frontal de ratos nutridos e desnutridos. 2022. 67 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Instituto de Saúde e Sociedade, Universidade Federal de São Paulo, Santos, 2022.