Neonatal D-fenfluramine treatment promotes long-term behavioral changes in adult mice

Autor(es)

Laureano-Melo, Roberto ; Dos-Santos, Raoni Conceicao ; da Conceicao, Rodrigo Rodrigues ; de Souza, Janaina Sena ; Almeida, Claudio da Silva ; Reis, Luis Carlos ; Marinho, Bruno Guimaraes ; Giannocco, Gisele ; Ahmed, Ragab Gaber ; Cortes, Wellington da Silva

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE; v. N/A, p. 13-pg., 2022-06-29.

Resumo

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of neonatal treatment of d-fenfluramine (d-FEN), a serotonin (5-HT) releaser, on the behavioral expression of adult male Swiss mice. For this purpose, we divided pregnant female Swiss mice into two groups (n = 6 each and similar to 35 g). Their off-spring were treated with d-FEN (3 mg/kg, s.c.) from postnatal days (PND) 5 to 20. At PND 21, one male puppy of each litter was euthanized; the midbrain and the hippocampus were dissected for RNA analysis. At PND 70, the male off-spring underwent a behavioral assessment in the open field, elevated plus-maze, light-dark box, tail suspension, and rotarod test. The programmed animals had a decrease in 5HT1a, serotonin transporter (SERT), and brain-derived neurotrophic factor (BDNF) expression in the mesencephalic raphe region. Alternatively, there was a reduction only in the tryptophan hydroxylase (TPH2) and BDNF expression in the hippocampus. In the light-dark box test, offspring of the treated group had higher latency to light and less time on the light side than the control. Also, it was observed less time of immobility in the tail suspension test. We also observed low motor skill learning in the rotarod test. These findings suggest that programming with d-FEN during the neonatal period alters a mesencephalic and hippocampal serotonergic system, promoting anxiety, antidepressant behavior, low coordination, and motor learning in adults. (AU)

• Processo FAPESP: 17/23169-1 - Efeito dos hormônios tiroidianos no encéfalo de camundongos 3xTg-AD (APPswe, PS1m146v, tauP301L) modelo da doença de Alzheimer
• Beneficiário: Gisele Giannocco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/22763-0 - DNA antigo, bioengenharia e "organoides" de cérebro: estudo da homeostase do hormônio tiroidiano e marcadores da Doença de Alzheimer em células tronco com gene NOVA1 editado por CRISPR
• Beneficiário: Janaína Sena de Souza
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 17/07053-3 - Efeito do hormônio tiroidiano no encéfalo de camundongos 3xTg-AD, modelo da Doença de Alzheimer, no metabolismo da glicose e colesterol
• Beneficiário: Janaína Sena de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado