title: Behavioral alterations and Fos protein immunoreactivity in brain regions of bile duct-ligated cirrhotic rats.
abstract: Hepatic encephalopathy (HE) encompasses a variety of neuropsychiatric symptoms, including anxiety and psychomotor dysfunction. Although HE is a frequent complication of liver cirrhosis, the neurobiological substrates responsible for its clinical manifestations are largely unclear. In the present study, male Wistar rats were bile duct-ligated (BDL), a procedure which induces liver cirrhosis, and on the 21st day after surgery tested in the elevated plus-maze (EPM) and in an open field for anxiety and locomotor activity measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to better understand the neurobiological alterations present in BDL animals. Plasma levels of ammonia were quantified and histopathological analysis of the livers was performed. BDL rats showed a significant decrease in the percentage of entries and time spent in the open arms of the EPM, an anxiogenic effect. These animals also presented significant decreases in Fos-ir in the lateral septal nucleus and medial amygdalar nucleus. Their ammonia plasma levels were significantly higher when compared to the sham group and the diagnosis of cirrhosis was confirmed by histopathological analysis. These results indicate that the BDL model induces anxiogenic results, possibly related to changes in the activation of anxiety-mediating circuitries and to increases in ammonia plasma levels.
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Le Sueur-Maluf
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Milena B
authors.initials: MB
authors.lastname: Viana
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Nagaoka
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Ana Laura B
authors.initials: AL
authors.lastname: Amorim
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Cardoso
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Rodrigues
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Natália F
authors.initials: NF
authors.lastname: Mendes
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brasil.
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Céspedes
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D001652:Bile Ducts / Q000601:surgery; D001923:Brain Chemistry / Q000502:physiology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008026:Ligation; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000641:Ammonia