Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction
Abstract There are many indications of a connection between abnormal glutamate transmission through N-methyl- d -aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its phy...
Gespeichert in:
Veröffentlicht in: | Psychiatry research. Neuroimaging 2016-02, Vol.248, p.1-11 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 11 |
---|---|
container_issue | |
container_start_page | 1 |
container_title | Psychiatry research. Neuroimaging |
container_volume | 248 |
creator | Kosten, Lauren Verhaeghe, Jeroen Verkerk, Robert Thomae, David De Picker, Livia wyffels, Leonie Van Eetveldt, Annemie Dedeurwaerdere, Stefanie Stroobants, Sigrid Staelens, Steven |
description | Abstract There are many indications of a connection between abnormal glutamate transmission through N-methyl- d -aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [11 C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [18 F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [18 F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression. |
doi_str_mv | 10.1016/j.pscychresns.2016.01.013 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1790964740</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0925492716300178</els_id><sourcerecordid>1765115050</sourcerecordid><originalsourceid>FETCH-LOGICAL-c586t-a31c1d8677feeff6fc68d399c79168ed7c5c53c6630015a6b9338ae855ed56323</originalsourceid><addsrcrecordid>eNqNkk9v1DAQxS0EotvCV0DmxiWLHa__XZCqLVCklh6As-V1JlsvThzsBCnfvk63rRCnSiNZsn9vRn5vEHpPyZoSKj4e1kN2s7tNkPu8rsvVmtBS7AVaUSXrSnIiXqIV0TWvNrqWJ-g05wMhNVOCvUYntVCEbaReIbiewuiHFHeAuxjATcEm7Du79_0exxbbHn-_vjjHCRwMY0z4dh5iO_Vu9LHHyY5F1kDAbXnah2m0nR0h7b3DzZwfuTfoVWtDhrcP5xn69eXzz-1ldXXz9dv2_KpyXImxsow62ighZQvQtqJ1QjVMayc1FQoa6bjjzAnBCKHcip1mTFlQnEPDBavZGfpw7Fs-9GeCPJrOZwch2B7ilA2VmmixkRvyDFRwSjnhC6qPqEsx5wStGVJxKM2GErMEYg7mn0DMEoghtBQr2ncPY6ZdB82T8jGBAmyPABRf_npIJjsPvYPGF8tH00T_rDGf_uvigu-9s-E3zJAPcUp9Md5Qk2tDzI9lM5bFoPdWSsXuAHrjuLo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1765115050</pqid></control><display><type>article</type><title>Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Kosten, Lauren ; Verhaeghe, Jeroen ; Verkerk, Robert ; Thomae, David ; De Picker, Livia ; wyffels, Leonie ; Van Eetveldt, Annemie ; Dedeurwaerdere, Stefanie ; Stroobants, Sigrid ; Staelens, Steven</creator><creatorcontrib>Kosten, Lauren ; Verhaeghe, Jeroen ; Verkerk, Robert ; Thomae, David ; De Picker, Livia ; wyffels, Leonie ; Van Eetveldt, Annemie ; Dedeurwaerdere, Stefanie ; Stroobants, Sigrid ; Staelens, Steven</creatorcontrib><description>Abstract There are many indications of a connection between abnormal glutamate transmission through N-methyl- d -aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [11 C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [18 F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [18 F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression.</description><identifier>ISSN: 0925-4927</identifier><identifier>EISSN: 1872-7506</identifier><identifier>DOI: 10.1016/j.pscychresns.2016.01.013</identifier><identifier>PMID: 26803479</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>Animal model ; Animals ; Brain - drug effects ; Brain - metabolism ; Disease Models, Animal ; Dizocilpine Maleate - administration & dosage ; Dizocilpine Maleate - pharmacology ; Excitatory Amino Acid Antagonists - administration & dosage ; Excitatory Amino Acid Antagonists - pharmacology ; Glutamate ; Glutamic Acid - metabolism ; Kynurenine - metabolism ; Male ; Molecular Imaging ; Positron-Emission Tomography - methods ; Psychiatry ; Radiology ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 - metabolism ; Receptors, N-Methyl-D-Aspartate - metabolism ; Schizophrenia ; Schizophrenia - metabolism ; TRYCAT ; Tryptophan - metabolism</subject><ispartof>Psychiatry research. Neuroimaging, 2016-02, Vol.248, p.1-11</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-a31c1d8677feeff6fc68d399c79168ed7c5c53c6630015a6b9338ae855ed56323</citedby><cites>FETCH-LOGICAL-c586t-a31c1d8677feeff6fc68d399c79168ed7c5c53c6630015a6b9338ae855ed56323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.pscychresns.2016.01.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26803479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kosten, Lauren</creatorcontrib><creatorcontrib>Verhaeghe, Jeroen</creatorcontrib><creatorcontrib>Verkerk, Robert</creatorcontrib><creatorcontrib>Thomae, David</creatorcontrib><creatorcontrib>De Picker, Livia</creatorcontrib><creatorcontrib>wyffels, Leonie</creatorcontrib><creatorcontrib>Van Eetveldt, Annemie</creatorcontrib><creatorcontrib>Dedeurwaerdere, Stefanie</creatorcontrib><creatorcontrib>Stroobants, Sigrid</creatorcontrib><creatorcontrib>Staelens, Steven</creatorcontrib><title>Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction</title><title>Psychiatry research. Neuroimaging</title><addtitle>Psychiatry Res Neuroimaging</addtitle><description>Abstract There are many indications of a connection between abnormal glutamate transmission through N-methyl- d -aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [11 C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [18 F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [18 F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression.</description><subject>Animal model</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Disease Models, Animal</subject><subject>Dizocilpine Maleate - administration & dosage</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - administration & dosage</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Glutamate</subject><subject>Glutamic Acid - metabolism</subject><subject>Kynurenine - metabolism</subject><subject>Male</subject><subject>Molecular Imaging</subject><subject>Positron-Emission Tomography - methods</subject><subject>Psychiatry</subject><subject>Radiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Metabotropic Glutamate 5 - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Schizophrenia</subject><subject>Schizophrenia - metabolism</subject><subject>TRYCAT</subject><subject>Tryptophan - metabolism</subject><issn>0925-4927</issn><issn>1872-7506</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk9v1DAQxS0EotvCV0DmxiWLHa__XZCqLVCklh6As-V1JlsvThzsBCnfvk63rRCnSiNZsn9vRn5vEHpPyZoSKj4e1kN2s7tNkPu8rsvVmtBS7AVaUSXrSnIiXqIV0TWvNrqWJ-g05wMhNVOCvUYntVCEbaReIbiewuiHFHeAuxjATcEm7Du79_0exxbbHn-_vjjHCRwMY0z4dh5iO_Vu9LHHyY5F1kDAbXnah2m0nR0h7b3DzZwfuTfoVWtDhrcP5xn69eXzz-1ldXXz9dv2_KpyXImxsow62ighZQvQtqJ1QjVMayc1FQoa6bjjzAnBCKHcip1mTFlQnEPDBavZGfpw7Fs-9GeCPJrOZwch2B7ilA2VmmixkRvyDFRwSjnhC6qPqEsx5wStGVJxKM2GErMEYg7mn0DMEoghtBQr2ncPY6ZdB82T8jGBAmyPABRf_npIJjsPvYPGF8tH00T_rDGf_uvigu-9s-E3zJAPcUp9Md5Qk2tDzI9lM5bFoPdWSsXuAHrjuLo</recordid><startdate>20160228</startdate><enddate>20160228</enddate><creator>Kosten, Lauren</creator><creator>Verhaeghe, Jeroen</creator><creator>Verkerk, Robert</creator><creator>Thomae, David</creator><creator>De Picker, Livia</creator><creator>wyffels, Leonie</creator><creator>Van Eetveldt, Annemie</creator><creator>Dedeurwaerdere, Stefanie</creator><creator>Stroobants, Sigrid</creator><creator>Staelens, Steven</creator><general>Elsevier Ireland Ltd</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>20160228</creationdate><title>Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction</title><author>Kosten, Lauren ; Verhaeghe, Jeroen ; Verkerk, Robert ; Thomae, David ; De Picker, Livia ; wyffels, Leonie ; Van Eetveldt, Annemie ; Dedeurwaerdere, Stefanie ; Stroobants, Sigrid ; Staelens, Steven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c586t-a31c1d8677feeff6fc68d399c79168ed7c5c53c6630015a6b9338ae855ed56323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animal model</topic><topic>Animals</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Disease Models, Animal</topic><topic>Dizocilpine Maleate - administration & dosage</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - administration & dosage</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Glutamate</topic><topic>Glutamic Acid - metabolism</topic><topic>Kynurenine - metabolism</topic><topic>Male</topic><topic>Molecular Imaging</topic><topic>Positron-Emission Tomography - methods</topic><topic>Psychiatry</topic><topic>Radiology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Metabotropic Glutamate 5 - metabolism</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Schizophrenia</topic><topic>Schizophrenia - metabolism</topic><topic>TRYCAT</topic><topic>Tryptophan - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kosten, Lauren</creatorcontrib><creatorcontrib>Verhaeghe, Jeroen</creatorcontrib><creatorcontrib>Verkerk, Robert</creatorcontrib><creatorcontrib>Thomae, David</creatorcontrib><creatorcontrib>De Picker, Livia</creatorcontrib><creatorcontrib>wyffels, Leonie</creatorcontrib><creatorcontrib>Van Eetveldt, Annemie</creatorcontrib><creatorcontrib>Dedeurwaerdere, Stefanie</creatorcontrib><creatorcontrib>Stroobants, Sigrid</creatorcontrib><creatorcontrib>Staelens, Steven</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Psychiatry research. Neuroimaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kosten, Lauren</au><au>Verhaeghe, Jeroen</au><au>Verkerk, Robert</au><au>Thomae, David</au><au>De Picker, Livia</au><au>wyffels, Leonie</au><au>Van Eetveldt, Annemie</au><au>Dedeurwaerdere, Stefanie</au><au>Stroobants, Sigrid</au><au>Staelens, Steven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction</atitle><jtitle>Psychiatry research. Neuroimaging</jtitle><addtitle>Psychiatry Res Neuroimaging</addtitle><date>2016-02-28</date><risdate>2016</risdate><volume>248</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0925-4927</issn><eissn>1872-7506</eissn><abstract>Abstract There are many indications of a connection between abnormal glutamate transmission through N-methyl- d -aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [11 C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [18 F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [18 F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>26803479</pmid><doi>10.1016/j.pscychresns.2016.01.013</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0925-4927 |
ispartof | Psychiatry research. Neuroimaging, 2016-02, Vol.248, p.1-11 |
issn | 0925-4927 1872-7506 |
language | eng |
recordid | cdi_proquest_miscellaneous_1790964740 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Animal model Animals Brain - drug effects Brain - metabolism Disease Models, Animal Dizocilpine Maleate - administration & dosage Dizocilpine Maleate - pharmacology Excitatory Amino Acid Antagonists - administration & dosage Excitatory Amino Acid Antagonists - pharmacology Glutamate Glutamic Acid - metabolism Kynurenine - metabolism Male Molecular Imaging Positron-Emission Tomography - methods Psychiatry Radiology Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 - metabolism Receptors, N-Methyl-D-Aspartate - metabolism Schizophrenia Schizophrenia - metabolism TRYCAT Tryptophan - metabolism |
title | Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T23%3A30%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiprobe%20molecular%20imaging%20of%20an%20NMDA%20receptor%20hypofunction%20rat%20model%20for%20glutamatergic%20dysfunction&rft.jtitle=Psychiatry%20research.%20Neuroimaging&rft.au=Kosten,%20Lauren&rft.date=2016-02-28&rft.volume=248&rft.spage=1&rft.epage=11&rft.pages=1-11&rft.issn=0925-4927&rft.eissn=1872-7506&rft_id=info:doi/10.1016/j.pscychresns.2016.01.013&rft_dat=%3Cproquest_cross%3E1765115050%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1765115050&rft_id=info:pmid/26803479&rft_els_id=S0925492716300178&rfr_iscdi=true |