Behavioral alterations and Fos protein immunoreactivity in brain regions of bile duct-ligated cirrhotic rats

• Published in: Anais da Academia Brasileira de Ciências Vol. 87; no. 1; pp. 331 - 341
• Main Authors: Le Sueur-Maluf, Luciana, Viana, Milena B, Nagaoka, Márcia R, Amorim, Ana Laura B, Cardoso, Amanda N, Rodrigues, Bruna C, Mendes, Natália F, Bittencourt, Jackson C, Céspedes, Isabel C
• Format: Journal Article
• Language: English
• Published: Brazil Academia Brasileira de Ciências 01.03.2015
• Subjects: Ammonia - blood; Animals; ansiedade; Anxiety - physiopathology; atividade locomotora; Behavior, Animal - physiology; Bile Ducts - surgery; Brain Chemistry - physiology; Disease Models, Animal; encefalopatia hepática; Immunohistochemistry; Ligation; ligação do ducto biliar; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Male; Motor Activity - physiology; MULTIDISCIPLINARY SCIENCES; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Wistar; anxiety; bile-duct ligation; Fos-immunoreactivity; hepatic encephalopathy; ansiedade; encefalopatia hepática; locomotor activity; ligação do ducto biliar; atividade locomotora
• ISSN: 0001-3765; 1678-2690; 1678-2690
• DOI: 10.1590/0001-3765201420130262

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.