Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice.

Autor: Fernandes HB; Laboratório de Genes Inflamatórios, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil; Laboratório de Neurobiologia, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil. Electronic address: helianadbf@gmail.com., Oliveira BDS; Laboratório de Neurobiologia, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., Machado CA; Laboratório de Neurobiologia, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., Carvalho BC; Laboratório de Genes Inflamatórios, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., de Brito Toscano EC; Laboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Av. Eugênio do Nascimento, s/n°, Dom Bosco, CEP: 36038-330, Juiz de Fora, MG, Brazil., da Silva MCM; Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., Vieira ÉLM; Campbell Family Mental Health Research Institute, Center of Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada., de Oliveira ACP; Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., Teixeira AL; Departament of Psychiatry and Behavioral Science McGovern School, Behavioral and Biomedical Sciences Building (BBSB), The University of Texas Health Science Center, 941 East Road, Houston, TX 77054, United States of America., de Miranda AS; Laboratório de Neurobiologia, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil., da Silva AM; Laboratório de Genes Inflamatórios, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, MG, Brazil.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2024 Feb 08; Vol. 129, pp. 110908. Date of Electronic Publication: 2023 Dec 02.
DOI: 10.1016/j.pnpbp.2023.110908
Abstrakt: The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning. Using RasGEF1b deficient mice (RasGEF1b-cKO), we investigated the impact of this gene deletion in behavior, cognition, brain neurochemistry and microglia morphology. We showed that RasGEF1b-cKO mice display spontaneous hyperlocomotion and anhedonia. RasGEF1b-cKO mice also exhibited compulsive-like behavior that was restored after acute treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (5 mg/kg). A down-regulation of mRNA of dopamine receptor (Drd1, Drd2, Drd4 and Drd5) and serotonin receptor genes (5Htr1a, 5Htr1b and 5Htr1d) was observed in hippocampus of RasGEF1b-cKO mice. These mice also had reduction of Drd1 and Drd2 in prefrontal cortex and 5Htr1d in striatum. In addition, morphological alterations were observed in RasGEF1b deficient microglia along with decreased levels of hippocampal BDNF. We provided original evidence that the deletion of RasGEF1b leads to unique behavioral features, implicating this factor in CNS functioning.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: