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dc.contributor.authorMendes, Natalia Ferreira [UNIFESP]
dc.contributor.authorMariotti, Flora Franca Nogueira [UNIFESP]
dc.contributor.authorAndrade, José Simões de [UNIFESP]
dc.contributor.authorViana, Milena de Barros [UNIFESP]
dc.contributor.authorCéspedes, Isabel Cristina [UNIFESP]
dc.contributor.authorNagaoka, Marcia Regina [UNIFESP]
dc.contributor.authorLe Sueur-Maluf, Luciana [UNIFESP]
dc.date.accessioned2020-09-01T13:21:13Z
dc.date.available2020-09-01T13:21:13Z
dc.date.issued2017
dc.identifierhttps://dx.doi.org/10.1007/s11011-017-0098-x
dc.identifier.citationMetabolic Brain Disease. New York, v. 32, n. 6, p. 2073-2083, 2017.
dc.identifier.issn0885-7490
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/58136
dc.description.abstractLactulose is a nonabsorbable disaccharide commonly used in clinical practice to treat hepatic encephalopathy. However, its effects on neuropsychiatric disorders and motor behavior have not been fully elucidated. Male Wistar rats were bile-duct ligated, and 3 weeks after surgery, treated with lactulose administrated by gavage (1.43 or 3.57 g/kg), once a day for seven days. Plasma levels of ammonia, aspartate aminotransferase, total bilirubin, and creatinine were quantified and histopathological analysis of the livers was performed. Locomotor activity measurements were performed in an open field. The expression of water channel aquaporin-4 was investigated and the analysis of Fos protein immunoreactivity was used to evaluate the pattern of neural activation in brain areas related to motor behavior. Bile-duct ligated rats showed hyperammonemia, loss of liver integrity and function, impaired locomotor activity, reduced aquaporin-4 protein expression, and neuronal hyperactivity. Lactulose treatment was able to reduce ammonia plasma levels, despite not having an effect on biochemical parameters of liver function, such as aspartate aminotransferase activity and total bilirubin levels, or on the cirrhotic hepatic architecture. Lactulose was also able to reduce the locomotor activity impairments and to mitigate or reverse most changes in neuronal activation. Lactulose had no effect on reduced aquaporin-4 protein expression. Our findings confirm the effectiveness of lactulose in reducing hyperammonemia and neuronal hyperactivity in brain areas related to motor behavior, reinforcing the importance of its clinical use in the treatment of the symptoms of cirrhosis-associated encephalopathy.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.format.extent2073-2083
dc.language.isoeng
dc.publisherSpringer/Plenum Publishers
dc.relation.ispartofMetabolic Brain Disease
dc.rightsAcesso aberto
dc.subjectHepatic encephalopathyen
dc.subjectBile-duct ligationen
dc.subjectLactuloseen
dc.subjectMotor behavioren
dc.titleLactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic ratsen
dc.typeArtigo
dc.description.affiliationUniv Fed Sao Paulo, Dept Biociencias, UNIFESP, 133-136 Vila Mathias, BR-11015020 Santos, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Lab Sinalizacao Celular, UNICAMP, BR-13083864 Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Morfol & Genet, UNIFESP, BR-11015020 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biociencias, UNIFESP, 133-136 Vila Mathias, BR-11015020 Santos, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Morfol & Genet, UNIFESP, BR-11015020 Sao Paulo, SP, Brazil
dc.description.sponsorshipIDFAPESP: 08/06450-0
dc.identifier.doi10.1007/s11011-017-0098-x
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000415225800031
dc.coverageNew York
dc.citation.volume32
dc.citation.issue6


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