Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats
Lactulose 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 lactulo...
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| Veröffentlicht in: | Metabolic brain disease 2017-12, Vol.32 (6), p.2073-2083 |
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| creator | Mendes, Natália Ferreira Mariotti, Flora França Nogueira de Andrade, José Simões de Barros Viana, Milena Céspedes, Isabel Cristina Nagaoka, Márcia Regina Le Sueur-Maluf, Luciana |
| description | Lactulose 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. |
| doi_str_mv | 10.1007/s11011-017-0098-x |
| format | Article |
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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.</description><identifier>ISSN: 0885-7490</identifier><identifier>EISSN: 1573-7365</identifier><identifier>DOI: 10.1007/s11011-017-0098-x</identifier><identifier>PMID: 28875419</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Activation ; Ammonia ; Ammonia - blood ; Animals ; Aquaporin 4 ; Aquaporin 4 - metabolism ; Aquaporins ; Aspartate aminotransferase ; Aspartate Aminotransferases - blood ; Behavior, Animal - drug effects ; Bilirubin ; Bilirubin - blood ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Cirrhosis ; Creatinine ; Creatinine - blood ; Disease Models, Animal ; Hepatic encephalopathy ; Hyperactivity ; Hyperammonemia ; Hyperammonemia - drug therapy ; Hyperammonemia - metabolism ; Hyperammonemia - pathology ; Immunoreactivity ; Lactulose ; Lactulose - pharmacology ; Lactulose - therapeutic use ; Liver ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver cirrhosis ; Locomotor activity ; Male ; Mental disorders ; Metabolic Diseases ; Motor Activity - drug effects ; Neurology ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; Neurosciences ; Oncology ; Original Article ; Plasma levels ; Protein expression ; Proteins ; Proto-Oncogene Proteins c-fos - metabolism ; Rats ; Rats, Wistar ; Rodents ; Surgery</subject><ispartof>Metabolic brain disease, 2017-12, Vol.32 (6), p.2073-2083</ispartof><rights>Springer Science+Business Media, LLC 2017</rights><rights>Metabolic Brain Disease is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-d5ea0a910351eac4ec79f9852df7b254bef8de42fefd161ab50c4e196f10e3633</citedby><cites>FETCH-LOGICAL-c372t-d5ea0a910351eac4ec79f9852df7b254bef8de42fefd161ab50c4e196f10e3633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11011-017-0098-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11011-017-0098-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28875419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mendes, Natália Ferreira</creatorcontrib><creatorcontrib>Mariotti, Flora França Nogueira</creatorcontrib><creatorcontrib>de Andrade, José Simões</creatorcontrib><creatorcontrib>de Barros Viana, Milena</creatorcontrib><creatorcontrib>Céspedes, Isabel Cristina</creatorcontrib><creatorcontrib>Nagaoka, Márcia Regina</creatorcontrib><creatorcontrib>Le Sueur-Maluf, Luciana</creatorcontrib><title>Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats</title><title>Metabolic brain disease</title><addtitle>Metab Brain Dis</addtitle><addtitle>Metab Brain Dis</addtitle><description>Lactulose 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.</description><subject>Activation</subject><subject>Ammonia</subject><subject>Ammonia - blood</subject><subject>Animals</subject><subject>Aquaporin 4</subject><subject>Aquaporin 4 - metabolism</subject><subject>Aquaporins</subject><subject>Aspartate aminotransferase</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Behavior, Animal - drug effects</subject><subject>Bilirubin</subject><subject>Bilirubin - blood</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Cirrhosis</subject><subject>Creatinine</subject><subject>Creatinine - blood</subject><subject>Disease Models, Animal</subject><subject>Hepatic encephalopathy</subject><subject>Hyperactivity</subject><subject>Hyperammonemia</subject><subject>Hyperammonemia - drug therapy</subject><subject>Hyperammonemia - metabolism</subject><subject>Hyperammonemia - pathology</subject><subject>Immunoreactivity</subject><subject>Lactulose</subject><subject>Lactulose - pharmacology</subject><subject>Lactulose - therapeutic use</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver cirrhosis</subject><subject>Locomotor activity</subject><subject>Male</subject><subject>Mental disorders</subject><subject>Metabolic Diseases</subject><subject>Motor Activity - drug effects</subject><subject>Neurology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurosciences</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Plasma levels</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-fos - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Surgery</subject><issn>0885-7490</issn><issn>1573-7365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc1u1TAQhS0EorctD8AGWWLDJuCx4zheoqpQpCt1064tx5m0rhL7YjtV-_Y4ugUhJFazON-c-TmEvAf2GRhTXzIAA2gYqIYx3TdPr8gOpBKNEp18TXas72WjWs1OyGnOD4wxIUG_JSe875VsQe_I3d66ss4xIx3RJbQZMw24phjsTKvmH23xMVAbRmpLwbDaUpEllpjogPf20cdU0REn73zJ1Ad6_3zAZJclBly8o8mWfE7eTHbO-O6lnpHbb5c3F1fN_vr7j4uv-8YJxUszSrTMatgWRetadEpPupd8nNTAZTvg1I_Y8gmnETqwg2QVAt1NwFB0QpyRT0ffQ4o_V8zFLD47nGcbMK7ZgBYd7zQXfUU__oM-xDXVszeq4woU45shHCmXYs4JJ3NIfrHp2QAzWwrmmIKpKZgtBfNUez68OK_DguOfjt9vrwA_ArlK4Q7TX6P_6_oLHoaVBg</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Mendes, Natália Ferreira</creator><creator>Mariotti, Flora França Nogueira</creator><creator>de Andrade, José Simões</creator><creator>de Barros Viana, Milena</creator><creator>Céspedes, Isabel Cristina</creator><creator>Nagaoka, Márcia Regina</creator><creator>Le Sueur-Maluf, Luciana</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20171201</creationdate><title>Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats</title><author>Mendes, Natália Ferreira ; Mariotti, Flora França Nogueira ; de Andrade, José Simões ; de Barros Viana, Milena ; Céspedes, Isabel Cristina ; Nagaoka, Márcia Regina ; Le Sueur-Maluf, Luciana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-d5ea0a910351eac4ec79f9852df7b254bef8de42fefd161ab50c4e196f10e3633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activation</topic><topic>Ammonia</topic><topic>Ammonia - blood</topic><topic>Animals</topic><topic>Aquaporin 4</topic><topic>Aquaporin 4 - metabolism</topic><topic>Aquaporins</topic><topic>Aspartate aminotransferase</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Behavior, Animal - drug effects</topic><topic>Bilirubin</topic><topic>Bilirubin - blood</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Cirrhosis</topic><topic>Creatinine</topic><topic>Creatinine - blood</topic><topic>Disease Models, Animal</topic><topic>Hepatic encephalopathy</topic><topic>Hyperactivity</topic><topic>Hyperammonemia</topic><topic>Hyperammonemia - drug therapy</topic><topic>Hyperammonemia - metabolism</topic><topic>Hyperammonemia - pathology</topic><topic>Immunoreactivity</topic><topic>Lactulose</topic><topic>Lactulose - pharmacology</topic><topic>Lactulose - therapeutic use</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver cirrhosis</topic><topic>Locomotor activity</topic><topic>Male</topic><topic>Mental disorders</topic><topic>Metabolic Diseases</topic><topic>Motor Activity - drug effects</topic><topic>Neurology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurosciences</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Plasma levels</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-fos - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mendes, Natália Ferreira</creatorcontrib><creatorcontrib>Mariotti, Flora França Nogueira</creatorcontrib><creatorcontrib>de Andrade, José Simões</creatorcontrib><creatorcontrib>de Barros Viana, Milena</creatorcontrib><creatorcontrib>Céspedes, Isabel Cristina</creatorcontrib><creatorcontrib>Nagaoka, Márcia Regina</creatorcontrib><creatorcontrib>Le Sueur-Maluf, Luciana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolic brain disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mendes, Natália Ferreira</au><au>Mariotti, Flora França Nogueira</au><au>de Andrade, José Simões</au><au>de Barros Viana, Milena</au><au>Céspedes, Isabel Cristina</au><au>Nagaoka, Márcia Regina</au><au>Le Sueur-Maluf, Luciana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats</atitle><jtitle>Metabolic brain disease</jtitle><stitle>Metab Brain Dis</stitle><addtitle>Metab Brain Dis</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>32</volume><issue>6</issue><spage>2073</spage><epage>2083</epage><pages>2073-2083</pages><issn>0885-7490</issn><eissn>1573-7365</eissn><abstract>Lactulose 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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28875419</pmid><doi>10.1007/s11011-017-0098-x</doi><tpages>11</tpages></addata></record> |
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| subjects | Activation Ammonia Ammonia - blood Animals Aquaporin 4 Aquaporin 4 - metabolism Aquaporins Aspartate aminotransferase Aspartate Aminotransferases - blood Behavior, Animal - drug effects Bilirubin Bilirubin - blood Biochemistry Biomedical and Life Sciences Biomedicine Brain Cirrhosis Creatinine Creatinine - blood Disease Models, Animal Hepatic encephalopathy Hyperactivity Hyperammonemia Hyperammonemia - drug therapy Hyperammonemia - metabolism Hyperammonemia - pathology Immunoreactivity Lactulose Lactulose - pharmacology Lactulose - therapeutic use Liver Liver - drug effects Liver - metabolism Liver - pathology Liver cirrhosis Locomotor activity Male Mental disorders Metabolic Diseases Motor Activity - drug effects Neurology Neurons - drug effects Neurons - metabolism Neurons - pathology Neurosciences Oncology Original Article Plasma levels Protein expression Proteins Proto-Oncogene Proteins c-fos - metabolism Rats Rats, Wistar Rodents Surgery |
| title | Lactulose decreases neuronal activation and attenuates motor behavioral deficits in hyperammonemic rats |
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