Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid
Abstract Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whet...
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| Veröffentlicht in: | Brain research 2016-01, Vol.1630, p.73-82 |
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| creator | Li, Cheng-Fu Chen, Xue-Mei Chen, Shao-Mei Mu, Rong-Hao Liu, Bin-Bin Luo, Liu Liu, Xiao-Long Geng, Di Liu, Qing Yi, Li-Tao |
| description | Abstract Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus. |
| doi_str_mv | 10.1016/j.brainres.2015.11.005 |
| format | Article |
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However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2015.11.005</identifier><identifier>PMID: 26562663</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>7-Chlorokynurenic acid ; Animals ; Antidepressive Agents - pharmacology ; Antidepressive Agents - toxicity ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - metabolism ; Depression ; Depressive Disorder - drug therapy ; Depressive Disorder - metabolism ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - pathology ; Kidney - drug effects ; Kidney - pathology ; Kynurenic Acid - analogs & derivatives ; Kynurenic Acid - pharmacology ; Kynurenic Acid - toxicity ; Liver - drug effects ; Liver - pathology ; Male ; MAP Kinase Signaling System - drug effects ; Mice, Inbred ICR ; Neurology ; Random Allocation ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - metabolism ; Stress, Psychological - drug therapy ; Stress, Psychological - metabolism ; Toxicological evaluation ; Uncertainty</subject><ispartof>Brain research, 2016-01, Vol.1630, p.73-82</ispartof><rights>Elsevier B.V.</rights><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-fc67213266803ab9e32fa43c28fe6d36047c9771804db5c304c4ecc49e9505f73</citedby><cites>FETCH-LOGICAL-c522t-fc67213266803ab9e32fa43c28fe6d36047c9771804db5c304c4ecc49e9505f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899315008483$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26562663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Cheng-Fu</creatorcontrib><creatorcontrib>Chen, Xue-Mei</creatorcontrib><creatorcontrib>Chen, Shao-Mei</creatorcontrib><creatorcontrib>Mu, Rong-Hao</creatorcontrib><creatorcontrib>Liu, Bin-Bin</creatorcontrib><creatorcontrib>Luo, Liu</creatorcontrib><creatorcontrib>Liu, Xiao-Long</creatorcontrib><creatorcontrib>Geng, Di</creatorcontrib><creatorcontrib>Liu, Qing</creatorcontrib><creatorcontrib>Yi, Li-Tao</creatorcontrib><title>Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus.</description><subject>7-Chlorokynurenic acid</subject><subject>Animals</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Antidepressive Agents - toxicity</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Depression</subject><subject>Depressive Disorder - drug therapy</subject><subject>Depressive Disorder - metabolism</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Kynurenic Acid - analogs & derivatives</subject><subject>Kynurenic Acid - pharmacology</subject><subject>Kynurenic Acid - toxicity</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mice, Inbred ICR</subject><subject>Neurology</subject><subject>Random Allocation</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Stress, Psychological - drug therapy</subject><subject>Stress, Psychological - metabolism</subject><subject>Toxicological evaluation</subject><subject>Uncertainty</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2P0zAQhi0EYsvCX1j5yCXBH4mTXBBlPwBpWQ7A2XInk9ZtagfbrdQfwX_GUXc5cOFgeSw9M-N33iHkirOSM67ebctVMNYFjKVgvC45Lxmrn5EFbxtRKFGx52TBGFNF23XygryKcZufUnbsJbkQqlZCKbkgv5eQ7NEk6x31A93YafJg9pMZ6cebhzsa7dqZ0bo1tZFad_TjEfsc0LRBalyyPU75EzGHxWh3SHEYENJcayYevt4saUDAKfkw82btnY2JNgVsRh_87uQOAZ0FasD2r8mLwYwR3zzel-Tn3e2P68_F_bdPX66X9wXUQqRiANUILrOClkmz6lCKwVQSRDug6qViVQNd0_CWVf2qBskqqBCg6rCrWT008pK8Pdedgv91wJj03kbAcTQO_SFq3tSyakQ-GVVnFIKPMeCgp2D3Jpw0Z3q2Qm_1kxV6tkJzrrMVOfHqscdhtcf-b9rT7DPw4QxgVnq0GHQEiw6wt3liSffe_r_H-39KQPbKghl3eMK49YeQ3ct6dBSa6e_zQsz7wGvG2qqV8g_9eLQx</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Li, Cheng-Fu</creator><creator>Chen, Xue-Mei</creator><creator>Chen, Shao-Mei</creator><creator>Mu, Rong-Hao</creator><creator>Liu, Bin-Bin</creator><creator>Luo, Liu</creator><creator>Liu, Xiao-Long</creator><creator>Geng, Di</creator><creator>Liu, Qing</creator><creator>Yi, Li-Tao</creator><general>Elsevier 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>7TK</scope></search><sort><creationdate>20160101</creationdate><title>Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid</title><author>Li, Cheng-Fu ; Chen, Xue-Mei ; Chen, Shao-Mei ; Mu, Rong-Hao ; Liu, Bin-Bin ; Luo, Liu ; Liu, Xiao-Long ; Geng, Di ; Liu, Qing ; Yi, Li-Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-fc67213266803ab9e32fa43c28fe6d36047c9771804db5c304c4ecc49e9505f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>7-Chlorokynurenic acid</topic><topic>Animals</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Antidepressive Agents - toxicity</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Depression</topic><topic>Depressive Disorder - drug therapy</topic><topic>Depressive Disorder - metabolism</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Kynurenic Acid - analogs & derivatives</topic><topic>Kynurenic Acid - pharmacology</topic><topic>Kynurenic Acid - toxicity</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mice, Inbred ICR</topic><topic>Neurology</topic><topic>Random Allocation</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Stress, Psychological - drug therapy</topic><topic>Stress, Psychological - metabolism</topic><topic>Toxicological evaluation</topic><topic>Uncertainty</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Cheng-Fu</creatorcontrib><creatorcontrib>Chen, Xue-Mei</creatorcontrib><creatorcontrib>Chen, Shao-Mei</creatorcontrib><creatorcontrib>Mu, Rong-Hao</creatorcontrib><creatorcontrib>Liu, Bin-Bin</creatorcontrib><creatorcontrib>Luo, Liu</creatorcontrib><creatorcontrib>Liu, Xiao-Long</creatorcontrib><creatorcontrib>Geng, Di</creatorcontrib><creatorcontrib>Liu, Qing</creatorcontrib><creatorcontrib>Yi, Li-Tao</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><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Cheng-Fu</au><au>Chen, Xue-Mei</au><au>Chen, Shao-Mei</au><au>Mu, Rong-Hao</au><au>Liu, Bin-Bin</au><au>Luo, Liu</au><au>Liu, Xiao-Long</au><au>Geng, Di</au><au>Liu, Qing</au><au>Yi, Li-Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>1630</volume><spage>73</spage><epage>82</epage><pages>73-82</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>Abstract Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26562663</pmid><doi>10.1016/j.brainres.2015.11.005</doi><tpages>10</tpages></addata></record> |
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| subjects | 7-Chlorokynurenic acid Animals Antidepressive Agents - pharmacology Antidepressive Agents - toxicity Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Depression Depressive Disorder - drug therapy Depressive Disorder - metabolism Disease Models, Animal Drug Evaluation, Preclinical Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Kidney - drug effects Kidney - pathology Kynurenic Acid - analogs & derivatives Kynurenic Acid - pharmacology Kynurenic Acid - toxicity Liver - drug effects Liver - pathology Male MAP Kinase Signaling System - drug effects Mice, Inbred ICR Neurology Random Allocation Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Stress, Psychological - drug therapy Stress, Psychological - metabolism Toxicological evaluation Uncertainty |
| title | Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid |
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