FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers
Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studie...
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Veröffentlicht in: | Molecular psychiatry 2015-02, Vol.20 (2), p.215-223 |
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description | Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders. |
doi_str_mv | 10.1038/mp.2013.192 |
format | Article |
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It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/mp.2013.192</identifier><identifier>PMID: 24468826</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/378/340 ; 692/699/375 ; 692/700/565/1436 ; Activation ; Aging ; AKT protein ; AKT1 protein ; Animals ; Animals, Newborn ; Antidepressants ; Antimanic Agents - pharmacology ; Behavioral Sciences ; Biological Psychology ; Brain-derived neurotrophic factor ; Cardiovascular disease ; Cells, Cultured ; Central nervous system ; Cerebral Cortex - cytology ; Diabetes ; Diabetes mellitus ; Drug Synergism ; Excitatory Amino Acid Agonists - toxicity ; Excitotoxicity ; Fibroblast growth factors ; Fibroblast Growth Factors - metabolism ; Fibroblast Growth Factors - pharmacology ; Gene Expression Regulation - drug effects ; Glucose metabolism ; Glutamic Acid - toxicity ; Glycogen ; Glycogen synthase kinase 3 ; Glycogen Synthase Kinase 3 - metabolism ; Glycogens ; Growth factors ; Health aspects ; Hippocampus - cytology ; Histone deacetylase ; Inhibitors ; Insulin resistance ; Kinases ; Lipid metabolism ; Lithium ; Lithium - pharmacology ; Lysates ; Male ; Medicine ; Medicine & Public Health ; Mental health ; Metabolic disorders ; Mice ; Mood ; mRNA ; Nervous system ; Neurobiology ; Neurons ; Neurons - drug effects ; Neuroprotection ; Neuroprotective Agents - metabolism ; Neuroprotective Agents - pharmacology ; Neurosciences ; Obesity ; Oncogene Protein v-akt - genetics ; Oncogene Protein v-akt - metabolism ; original-article ; Pharmacotherapy ; Physiological aspects ; Proteins ; Psychiatry ; Psychotropic drugs ; Rats ; Rats, Sprague-Dawley ; Synergistic effect ; Therapeutic applications ; Transduction, Genetic ; Valproic acid ; Valproic Acid - pharmacology ; Weight control</subject><ispartof>Molecular psychiatry, 2015-02, Vol.20 (2), p.215-223</ispartof><rights>Macmillan Publishers Limited 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-dcf52e5f7f6e6cc5fa82829de86ee519efb23c917f3cd2d30d527fa428be2d203</citedby><cites>FETCH-LOGICAL-c659t-dcf52e5f7f6e6cc5fa82829de86ee519efb23c917f3cd2d30d527fa428be2d203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/mp.2013.192$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/mp.2013.192$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24468826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leng, Y</creatorcontrib><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Tsai, L-K</creatorcontrib><creatorcontrib>Leeds, P</creatorcontrib><creatorcontrib>Fessler, E B</creatorcontrib><creatorcontrib>Wang, J</creatorcontrib><creatorcontrib>Chuang, D-M</creatorcontrib><title>FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.</description><subject>631/378/340</subject><subject>692/699/375</subject><subject>692/700/565/1436</subject><subject>Activation</subject><subject>Aging</subject><subject>AKT protein</subject><subject>AKT1 protein</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antidepressants</subject><subject>Antimanic Agents - pharmacology</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Brain-derived neurotrophic factor</subject><subject>Cardiovascular disease</subject><subject>Cells, Cultured</subject><subject>Central nervous system</subject><subject>Cerebral Cortex - cytology</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Drug Synergism</subject><subject>Excitatory Amino Acid Agonists - toxicity</subject><subject>Excitotoxicity</subject><subject>Fibroblast growth factors</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fibroblast Growth Factors - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucose metabolism</subject><subject>Glutamic Acid - toxicity</subject><subject>Glycogen</subject><subject>Glycogen synthase kinase 3</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogens</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Hippocampus - cytology</subject><subject>Histone deacetylase</subject><subject>Inhibitors</subject><subject>Insulin resistance</subject><subject>Kinases</subject><subject>Lipid metabolism</subject><subject>Lithium</subject><subject>Lithium - pharmacology</subject><subject>Lysates</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental health</subject><subject>Metabolic disorders</subject><subject>Mice</subject><subject>Mood</subject><subject>mRNA</subject><subject>Nervous system</subject><subject>Neurobiology</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - metabolism</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurosciences</subject><subject>Obesity</subject><subject>Oncogene Protein v-akt - genetics</subject><subject>Oncogene Protein v-akt - metabolism</subject><subject>original-article</subject><subject>Pharmacotherapy</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Psychiatry</subject><subject>Psychotropic drugs</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Synergistic effect</subject><subject>Therapeutic applications</subject><subject>Transduction, Genetic</subject><subject>Valproic acid</subject><subject>Valproic Acid - pharmacology</subject><subject>Weight control</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kk2LFDEQhhtR3HX15F0CXgSnx3x00unjsjirsOBFzyGdVMas6WRMugfGg7_dDLN-skgOCVVPVb0p3qZ5TvCaYCbfTLs1xYStyUAfNOek60XLeS8f1jfjQ9sR2Z01T0q5xfiY5I-bM9p1Qkoqzpvvm-tNS8kKaRTTHgKaYNZjCt6gDNsl6DnlFfqsSwVyGpcyowhLTrucZjCz30MNB0A6WuQLmnT-AjYcEATY6xlqMJ4KYkHjAU0pWVTqBB_8N8jlafPI6VDg2d190XzavP149a69-XD9_urypjWCD3NrjeMUuOudAGEMd1pSSQcLUgBwMoAbKTMD6R0zllqGLae90x2VI1BLMbtoXp36Vt1fFyizmnwxEIKOkJaiiJCMdQPFsqIv_0Fv05JjVacoY0TUXfP_UkQIfGT64Te11QGUjy7NWZvjaHXZ4Y4PtGqr1Poeqh4LkzcpgvM1_lfB61OByamUDE7tsq-rPyiC1dETatqpoydU9USlX9xJXcYJ7C_2pwkqsDoBpabiFvIff7mn3w9UAr6J</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Leng, Y</creator><creator>Wang, Z</creator><creator>Tsai, L-K</creator><creator>Leeds, P</creator><creator>Fessler, E B</creator><creator>Wang, J</creator><creator>Chuang, D-M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20150201</creationdate><title>FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers</title><author>Leng, Y ; Wang, Z ; Tsai, L-K ; Leeds, P ; Fessler, E B ; Wang, J ; Chuang, D-M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-dcf52e5f7f6e6cc5fa82829de86ee519efb23c917f3cd2d30d527fa428be2d203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/378/340</topic><topic>692/699/375</topic><topic>692/700/565/1436</topic><topic>Activation</topic><topic>Aging</topic><topic>AKT protein</topic><topic>AKT1 protein</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antidepressants</topic><topic>Antimanic Agents - pharmacology</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Brain-derived neurotrophic factor</topic><topic>Cardiovascular disease</topic><topic>Cells, Cultured</topic><topic>Central nervous system</topic><topic>Cerebral Cortex - cytology</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Drug Synergism</topic><topic>Excitatory Amino Acid Agonists - toxicity</topic><topic>Excitotoxicity</topic><topic>Fibroblast growth factors</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblast Growth Factors - pharmacology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucose metabolism</topic><topic>Glutamic Acid - toxicity</topic><topic>Glycogen</topic><topic>Glycogen synthase kinase 3</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogens</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Hippocampus - cytology</topic><topic>Histone deacetylase</topic><topic>Inhibitors</topic><topic>Insulin resistance</topic><topic>Kinases</topic><topic>Lipid metabolism</topic><topic>Lithium</topic><topic>Lithium - pharmacology</topic><topic>Lysates</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental health</topic><topic>Metabolic disorders</topic><topic>Mice</topic><topic>Mood</topic><topic>mRNA</topic><topic>Nervous system</topic><topic>Neurobiology</topic><topic>Neurons</topic><topic>Neurons - drug effects</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - metabolism</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neurosciences</topic><topic>Obesity</topic><topic>Oncogene Protein v-akt - genetics</topic><topic>Oncogene Protein v-akt - metabolism</topic><topic>original-article</topic><topic>Pharmacotherapy</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Psychiatry</topic><topic>Psychotropic drugs</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Synergistic effect</topic><topic>Therapeutic applications</topic><topic>Transduction, Genetic</topic><topic>Valproic acid</topic><topic>Valproic Acid - pharmacology</topic><topic>Weight control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leng, Y</creatorcontrib><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Tsai, L-K</creatorcontrib><creatorcontrib>Leeds, P</creatorcontrib><creatorcontrib>Fessler, E B</creatorcontrib><creatorcontrib>Wang, J</creatorcontrib><creatorcontrib>Chuang, D-M</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>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>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leng, Y</au><au>Wang, Z</au><au>Tsai, L-K</au><au>Leeds, P</au><au>Fessler, E B</au><au>Wang, J</au><au>Chuang, D-M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>20</volume><issue>2</issue><spage>215</spage><epage>223</epage><pages>215-223</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24468826</pmid><doi>10.1038/mp.2013.192</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/378/340 692/699/375 692/700/565/1436 Activation Aging AKT protein AKT1 protein Animals Animals, Newborn Antidepressants Antimanic Agents - pharmacology Behavioral Sciences Biological Psychology Brain-derived neurotrophic factor Cardiovascular disease Cells, Cultured Central nervous system Cerebral Cortex - cytology Diabetes Diabetes mellitus Drug Synergism Excitatory Amino Acid Agonists - toxicity Excitotoxicity Fibroblast growth factors Fibroblast Growth Factors - metabolism Fibroblast Growth Factors - pharmacology Gene Expression Regulation - drug effects Glucose metabolism Glutamic Acid - toxicity Glycogen Glycogen synthase kinase 3 Glycogen Synthase Kinase 3 - metabolism Glycogens Growth factors Health aspects Hippocampus - cytology Histone deacetylase Inhibitors Insulin resistance Kinases Lipid metabolism Lithium Lithium - pharmacology Lysates Male Medicine Medicine & Public Health Mental health Metabolic disorders Mice Mood mRNA Nervous system Neurobiology Neurons Neurons - drug effects Neuroprotection Neuroprotective Agents - metabolism Neuroprotective Agents - pharmacology Neurosciences Obesity Oncogene Protein v-akt - genetics Oncogene Protein v-akt - metabolism original-article Pharmacotherapy Physiological aspects Proteins Psychiatry Psychotropic drugs Rats Rats, Sprague-Dawley Synergistic effect Therapeutic applications Transduction, Genetic Valproic acid Valproic Acid - pharmacology Weight control |
title | FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers |
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