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Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats
We investigated the effect of valproate (ip, 500 mg/kg), which is regarded as a potent plasma protein tryptophan (TRP) displacer, on the central nervous system (hippocampal) and peripheral (plasma) levels of the aromatic amino acids (AAAs; e.g. TRP, tyrosine and phenylalanine) and branched-chain ami...
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| Published in: | Neurotoxicity research 2014-05, Vol.25 (4), p.358-368 |
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| cites | cdi_FETCH-LOGICAL-c377t-f12a2411f52b0f9090b6c42e39dcc7b877be847323255d5f18d2b01e25b22b9c3 |
| container_end_page | 368 |
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| container_title | Neurotoxicity research |
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| creator | Maciejak, Piotr Szyndler, Janusz Kołosowska, Karolina Turzyńska, Danuta Sobolewska, Alicja Walkowiak, Jerzy Płaźnik, Adam |
| description | We investigated the effect of valproate (ip, 500 mg/kg), which is regarded as a potent plasma protein tryptophan (TRP) displacer, on the central nervous system (hippocampal) and peripheral (plasma) levels of the aromatic amino acids (AAAs; e.g. TRP, tyrosine and phenylalanine) and branched-chain amino acids (BCAAs; e.g. valine, isoleucine and leucine) as well as the other amino acids (glutamate, GABA, alanine, glutamine, glycine, aspartate and taurine) involved in the regulation of neurotransmission. Furthermore, we investigated whether the changes in the BCAA/AAA ratio affected the hippocampal concentration of monoamines [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)]. Valproic acid (VPA) administration potently modified the balance between the BCAA and AAA. In the brain, the significantly increased AAA and decreased BCAA concentrations were followed by a decrease in the BCAA/AAA ratio. In the plasma, VPA significantly decreased the BCAA and AAA levels. The changes in the BCAA and AAA levels were accompanied by an increase in the NA, DA and 5-HT levels as well as hippocampal 5-HT metabolism. This novel finding indicates that VPA, through the displacement of TRP from its protein-binding sites, could disturb the BCAA/AAA ratio, with central nervous system consequences, including the possible contribution to VPAs effects in affective disorders. |
| doi_str_mv | 10.1007/s12640-013-9441-0 |
| format | article |
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Furthermore, we investigated whether the changes in the BCAA/AAA ratio affected the hippocampal concentration of monoamines [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)]. Valproic acid (VPA) administration potently modified the balance between the BCAA and AAA. In the brain, the significantly increased AAA and decreased BCAA concentrations were followed by a decrease in the BCAA/AAA ratio. In the plasma, VPA significantly decreased the BCAA and AAA levels. The changes in the BCAA and AAA levels were accompanied by an increase in the NA, DA and 5-HT levels as well as hippocampal 5-HT metabolism. This novel finding indicates that VPA, through the displacement of TRP from its protein-binding sites, could disturb the BCAA/AAA ratio, with central nervous system consequences, including the possible contribution to VPAs effects in affective disorders.</description><identifier>ISSN: 1029-8428</identifier><identifier>EISSN: 1476-3524</identifier><identifier>DOI: 10.1007/s12640-013-9441-0</identifier><identifier>PMID: 24249529</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Amino Acids - blood ; Amino Acids - metabolism ; Amino Acids, Aromatic - blood ; Amino Acids, Aromatic - metabolism ; Amino Acids, Branched-Chain - blood ; Amino Acids, Branched-Chain - metabolism ; Animals ; Antimanic Agents - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Male ; Neurobiology ; Neurochemistry ; Neurology ; Neurosciences ; Original Article ; Pharmacology/Toxicology ; Rats ; Rats, Wistar ; Tryptophan - blood ; Tryptophan - metabolism ; Valproic Acid - pharmacology</subject><ispartof>Neurotoxicity research, 2014-05, Vol.25 (4), p.358-368</ispartof><rights>Springer Science+Business Media New York 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-f12a2411f52b0f9090b6c42e39dcc7b877be847323255d5f18d2b01e25b22b9c3</citedby><cites>FETCH-LOGICAL-c377t-f12a2411f52b0f9090b6c42e39dcc7b877be847323255d5f18d2b01e25b22b9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24249529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maciejak, Piotr</creatorcontrib><creatorcontrib>Szyndler, Janusz</creatorcontrib><creatorcontrib>Kołosowska, Karolina</creatorcontrib><creatorcontrib>Turzyńska, Danuta</creatorcontrib><creatorcontrib>Sobolewska, Alicja</creatorcontrib><creatorcontrib>Walkowiak, Jerzy</creatorcontrib><creatorcontrib>Płaźnik, Adam</creatorcontrib><title>Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats</title><title>Neurotoxicity research</title><addtitle>Neurotox Res</addtitle><addtitle>Neurotox Res</addtitle><description>We investigated the effect of valproate (ip, 500 mg/kg), which is regarded as a potent plasma protein tryptophan (TRP) displacer, on the central nervous system (hippocampal) and peripheral (plasma) levels of the aromatic amino acids (AAAs; e.g. TRP, tyrosine and phenylalanine) and branched-chain amino acids (BCAAs; e.g. valine, isoleucine and leucine) as well as the other amino acids (glutamate, GABA, alanine, glutamine, glycine, aspartate and taurine) involved in the regulation of neurotransmission. Furthermore, we investigated whether the changes in the BCAA/AAA ratio affected the hippocampal concentration of monoamines [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)]. Valproic acid (VPA) administration potently modified the balance between the BCAA and AAA. In the brain, the significantly increased AAA and decreased BCAA concentrations were followed by a decrease in the BCAA/AAA ratio. In the plasma, VPA significantly decreased the BCAA and AAA levels. The changes in the BCAA and AAA levels were accompanied by an increase in the NA, DA and 5-HT levels as well as hippocampal 5-HT metabolism. This novel finding indicates that VPA, through the displacement of TRP from its protein-binding sites, could disturb the BCAA/AAA ratio, with central nervous system consequences, including the possible contribution to VPAs effects in affective disorders.</description><subject>Amino Acids - blood</subject><subject>Amino Acids - metabolism</subject><subject>Amino Acids, Aromatic - blood</subject><subject>Amino Acids, Aromatic - metabolism</subject><subject>Amino Acids, Branched-Chain - blood</subject><subject>Amino Acids, Branched-Chain - metabolism</subject><subject>Animals</subject><subject>Antimanic Agents - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Male</subject><subject>Neurobiology</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Tryptophan - blood</subject><subject>Tryptophan - metabolism</subject><subject>Valproic Acid - pharmacology</subject><issn>1029-8428</issn><issn>1476-3524</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAQRS0EoqXwAWyQl2wC9sSO42VbnlIlEAK2luM4NFUexXaE-HtcpbBkNTPymavxQeickitKiLj2FDJGEkLTRDJGE3KAppSJLEk5sMPYE5BJziCfoBPvN4QA5Zk4RhNgwCQHOUXP77rZul4Hi29qHwZXeBzWFi90ozsTqw1f1nZ44eK4tiXWXYnnrm91qA2et3XX47mpS4_rDr_o4E_RUaUbb8_2dYbe7m5flw_J6un-cTlfJSYVIiQVBQ2M0opDQSpJJCkyw8CmsjRGFLkQhc2ZSCEFzkte0byMILXAC4BCmnSGLsfceP3nYH1Qbe2NbeLZth-8ojxlOXAqs4jSETWu997ZSm1d3Wr3rShRO5FqFKmiSLUTqUjcudjHD0Vry7-NX3MRgBHw8an7sE5t-sF18cv_pP4A-Ml8Pw</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Maciejak, Piotr</creator><creator>Szyndler, Janusz</creator><creator>Kołosowska, Karolina</creator><creator>Turzyńska, Danuta</creator><creator>Sobolewska, Alicja</creator><creator>Walkowiak, Jerzy</creator><creator>Płaźnik, Adam</creator><general>Springer US</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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20140501</creationdate><title>Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats</title><author>Maciejak, Piotr ; Szyndler, Janusz ; Kołosowska, Karolina ; Turzyńska, Danuta ; Sobolewska, Alicja ; Walkowiak, Jerzy ; Płaźnik, Adam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-f12a2411f52b0f9090b6c42e39dcc7b877be847323255d5f18d2b01e25b22b9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amino Acids - blood</topic><topic>Amino Acids - metabolism</topic><topic>Amino Acids, Aromatic - blood</topic><topic>Amino Acids, Aromatic - metabolism</topic><topic>Amino Acids, Branched-Chain - blood</topic><topic>Amino Acids, Branched-Chain - metabolism</topic><topic>Animals</topic><topic>Antimanic Agents - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Male</topic><topic>Neurobiology</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Tryptophan - blood</topic><topic>Tryptophan - metabolism</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maciejak, Piotr</creatorcontrib><creatorcontrib>Szyndler, Janusz</creatorcontrib><creatorcontrib>Kołosowska, Karolina</creatorcontrib><creatorcontrib>Turzyńska, Danuta</creatorcontrib><creatorcontrib>Sobolewska, Alicja</creatorcontrib><creatorcontrib>Walkowiak, Jerzy</creatorcontrib><creatorcontrib>Płaźnik, Adam</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neurotoxicity research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maciejak, Piotr</au><au>Szyndler, Janusz</au><au>Kołosowska, Karolina</au><au>Turzyńska, Danuta</au><au>Sobolewska, Alicja</au><au>Walkowiak, Jerzy</au><au>Płaźnik, Adam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats</atitle><jtitle>Neurotoxicity research</jtitle><stitle>Neurotox Res</stitle><addtitle>Neurotox Res</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>25</volume><issue>4</issue><spage>358</spage><epage>368</epage><pages>358-368</pages><issn>1029-8428</issn><eissn>1476-3524</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><abstract>We investigated the effect of valproate (ip, 500 mg/kg), which is regarded as a potent plasma protein tryptophan (TRP) displacer, on the central nervous system (hippocampal) and peripheral (plasma) levels of the aromatic amino acids (AAAs; e.g. TRP, tyrosine and phenylalanine) and branched-chain amino acids (BCAAs; e.g. valine, isoleucine and leucine) as well as the other amino acids (glutamate, GABA, alanine, glutamine, glycine, aspartate and taurine) involved in the regulation of neurotransmission. Furthermore, we investigated whether the changes in the BCAA/AAA ratio affected the hippocampal concentration of monoamines [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)]. Valproic acid (VPA) administration potently modified the balance between the BCAA and AAA. In the brain, the significantly increased AAA and decreased BCAA concentrations were followed by a decrease in the BCAA/AAA ratio. In the plasma, VPA significantly decreased the BCAA and AAA levels. The changes in the BCAA and AAA levels were accompanied by an increase in the NA, DA and 5-HT levels as well as hippocampal 5-HT metabolism. This novel finding indicates that VPA, through the displacement of TRP from its protein-binding sites, could disturb the BCAA/AAA ratio, with central nervous system consequences, including the possible contribution to VPAs effects in affective disorders.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>24249529</pmid><doi>10.1007/s12640-013-9441-0</doi><tpages>11</tpages></addata></record> |
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| subjects | Amino Acids - blood Amino Acids - metabolism Amino Acids, Aromatic - blood Amino Acids, Aromatic - metabolism Amino Acids, Branched-Chain - blood Amino Acids, Branched-Chain - metabolism Animals Antimanic Agents - pharmacology Biomedical and Life Sciences Biomedicine Cell Biology Hippocampus - drug effects Hippocampus - metabolism Male Neurobiology Neurochemistry Neurology Neurosciences Original Article Pharmacology/Toxicology Rats Rats, Wistar Tryptophan - blood Tryptophan - metabolism Valproic Acid - pharmacology |
| title | Valproate Disturbs the Balance Between Branched and Aromatic Amino Acids in Rats |
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