TY - JOUR
T1 - Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice
AU - Fernandes, Heliana de Barros
AU - Oliveira, Bruna da Silva
AU - Machado, Caroline Amaral
AU - Carvalho, Brener Cunha
AU - de Brito Toscano, Eliana Cristina
AU - da Silva, Maria Carolina M.
AU - Vieira, Érica Leandro Marciano
AU - de Oliveira, Antônio Carlos Pinheiro
AU - Teixeira, Antônio Lúcio
AU - de Miranda, Aline Silva
AU - da Silva, Aristóbolo Mendes
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/2/8
Y1 - 2024/2/8
N2 - 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.
AB - 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.
KW - Anhedonia
KW - Compulsive-like behavior
KW - Hyperactivity
KW - Microglia
KW - RasGEF1b
UR - https://www.scopus.com/pages/publications/85179154814
UR - https://www.scopus.com/pages/publications/85179154814#tab=citedBy
U2 - 10.1016/j.pnpbp.2023.110908
DO - 10.1016/j.pnpbp.2023.110908
M3 - Article
C2 - 38048936
AN - SCOPUS:85179154814
SN - 0278-5846
VL - 129
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 110908
ER -