Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease
Adenosine A(₂A) receptor antagonism provides a promising approach to developing nondopaminergic therapy for Parkinson's disease (PD). Clinical trials of A(₂A) antagonists have targeted PD patients with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve parkin...
Gespeichert in:
| Veröffentlicht in: | Brain research 2011-01, Vol.1367, p.310 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 310 |
| container_title | Brain research |
| container_volume | 1367 |
| creator | Xiao, Danqing Cassin, Jared J Healy, Brian Burdett, Thomas C Chen, Jiang-Fan Fredholm, Bertil B Schwarzschild, Michael A |
| description | Adenosine A(₂A) receptor antagonism provides a promising approach to developing nondopaminergic therapy for Parkinson's disease (PD). Clinical trials of A(₂A) antagonists have targeted PD patients with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve parkinsonian symptoms. The role of adenosine in the development of LID is little known, especially regarding its actions via A₁ receptors. We aimed to examine the effects of genetic deletion and pharmacological blockade of A₁ and/or A(₂A) receptors on the development of LID, on the induction of molecular markers of LID including striatal preprodynorphin and preproenkephalin (PPE), and on the integrity of dopaminergic nigrostriatal neurons in hemiparkinsonian mice. Following a unilateral 6-hydroxydopamine lesion A₁, A(₂A) and double A₁-A(₂A) knockout (KO) and wild-type littermate mice, and mice pretreated with caffeine (an antagonist of both A₁ and A(₂A) receptors) or saline were treated daily for 18-21 days with a low dose of L-DOPA. Total abnormal involuntary movements (AIMs, a measure of LID) were significantly attenuated (p |
| doi_str_mv | 10.1016/j.brainres.2010.08.099 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed</sourceid><recordid>TN_cdi_pubmed_primary_20828543</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20828543</sourcerecordid><originalsourceid>FETCH-LOGICAL-p553-f0aafbeacbc4ffbe2d5fb033f40e27605a16277731ffc4e80212b84830dd004e3</originalsourceid><addsrcrecordid>eNo1UMtOwzAQtJAQLYVfqHwDJBI2tvPoMeItVYJD75UTr1WX1I7sViJHeuM3-yW4Ak47Ozu7ox1CphmkGWTF3TptvDTWY0gZRBKqFGazEzLOqpIlBRMwIuchrAGA8xmckRGDilW54GPy_YAdbo2z1GkqFVoXjEVaH_Zf1HlaXx_2-_qGemyx3zofIlK7FgOdJ_xWJMqsBuXd59Cv0A6d7KSN64mxR5GiaggfsQ9GUmOppBunsDs6vUsfB8HZq0CVCSgDXpBTLbuAl391QhZPj4v7l2T-9vx6X8-TPs95okFK3aBsm1boCJjKdRPf0gKQlQXkMitYWZY807oVWAHLWFOJioNSAAL5hEx_z_a7ZoNq2XuzkX5Y_kfCfwDrxWep</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Xiao, Danqing ; Cassin, Jared J ; Healy, Brian ; Burdett, Thomas C ; Chen, Jiang-Fan ; Fredholm, Bertil B ; Schwarzschild, Michael A</creator><creatorcontrib>Xiao, Danqing ; Cassin, Jared J ; Healy, Brian ; Burdett, Thomas C ; Chen, Jiang-Fan ; Fredholm, Bertil B ; Schwarzschild, Michael A</creatorcontrib><description>Adenosine A(₂A) receptor antagonism provides a promising approach to developing nondopaminergic therapy for Parkinson's disease (PD). Clinical trials of A(₂A) antagonists have targeted PD patients with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve parkinsonian symptoms. The role of adenosine in the development of LID is little known, especially regarding its actions via A₁ receptors. We aimed to examine the effects of genetic deletion and pharmacological blockade of A₁ and/or A(₂A) receptors on the development of LID, on the induction of molecular markers of LID including striatal preprodynorphin and preproenkephalin (PPE), and on the integrity of dopaminergic nigrostriatal neurons in hemiparkinsonian mice. Following a unilateral 6-hydroxydopamine lesion A₁, A(₂A) and double A₁-A(₂A) knockout (KO) and wild-type littermate mice, and mice pretreated with caffeine (an antagonist of both A₁ and A(₂A) receptors) or saline were treated daily for 18-21 days with a low dose of L-DOPA. Total abnormal involuntary movements (AIMs, a measure of LID) were significantly attenuated (p<0.05) in A₁ and A(₂A) KOs, but not in A₁-A(₂A) KOs and caffeine-pretreated mice. An elevation of PPE mRNA ipsilateral to the lesion in WT mice was reduced in all KO mice. In addition, neuronal integrity assessed by striatal dopamine content was similar in all KOs and caffeine-pretreated mice following 6-hydroxydopamine lesioning. Our findings raise the possibility that A₁ or A(₂A) receptors blockade might also confer a disease-modifying benefit of reduced risk of disabling LID, whereas the effect of their combined inactivation is less clear.</description><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2010.08.099</identifier><identifier>PMID: 20828543</identifier><language>eng</language><publisher>Netherlands</publisher><subject>Adrenergic Agents - toxicity ; Animals ; Antiparkinson Agents - adverse effects ; Caffeine - administration & dosage ; Corpus Striatum - drug effects ; Disease Models, Animal ; Dynorphins - genetics ; Dynorphins - metabolism ; Dyskinesia, Drug-Induced - etiology ; Dyskinesia, Drug-Induced - genetics ; Dyskinesia, Drug-Induced - prevention & control ; Enkephalins - genetics ; Enkephalins - metabolism ; Gene Expression Regulation - drug effects ; Levodopa - adverse effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidopamine - toxicity ; Parkinson Disease - drug therapy ; Parkinson Disease - etiology ; Parkinson Disease - genetics ; Protein Precursors - genetics ; Protein Precursors - metabolism ; Purinergic P1 Receptor Antagonists - administration & dosage ; Receptor, Adenosine A1 - deficiency ; Receptor, Adenosine A2A - deficiency ; RNA, Messenger - metabolism ; Statistics, Nonparametric ; Time Factors</subject><ispartof>Brain research, 2011-01, Vol.1367, p.310</ispartof><rights>Copyright © 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20828543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Danqing</creatorcontrib><creatorcontrib>Cassin, Jared J</creatorcontrib><creatorcontrib>Healy, Brian</creatorcontrib><creatorcontrib>Burdett, Thomas C</creatorcontrib><creatorcontrib>Chen, Jiang-Fan</creatorcontrib><creatorcontrib>Fredholm, Bertil B</creatorcontrib><creatorcontrib>Schwarzschild, Michael A</creatorcontrib><title>Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Adenosine A(₂A) receptor antagonism provides a promising approach to developing nondopaminergic therapy for Parkinson's disease (PD). Clinical trials of A(₂A) antagonists have targeted PD patients with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve parkinsonian symptoms. The role of adenosine in the development of LID is little known, especially regarding its actions via A₁ receptors. We aimed to examine the effects of genetic deletion and pharmacological blockade of A₁ and/or A(₂A) receptors on the development of LID, on the induction of molecular markers of LID including striatal preprodynorphin and preproenkephalin (PPE), and on the integrity of dopaminergic nigrostriatal neurons in hemiparkinsonian mice. Following a unilateral 6-hydroxydopamine lesion A₁, A(₂A) and double A₁-A(₂A) knockout (KO) and wild-type littermate mice, and mice pretreated with caffeine (an antagonist of both A₁ and A(₂A) receptors) or saline were treated daily for 18-21 days with a low dose of L-DOPA. Total abnormal involuntary movements (AIMs, a measure of LID) were significantly attenuated (p<0.05) in A₁ and A(₂A) KOs, but not in A₁-A(₂A) KOs and caffeine-pretreated mice. An elevation of PPE mRNA ipsilateral to the lesion in WT mice was reduced in all KO mice. In addition, neuronal integrity assessed by striatal dopamine content was similar in all KOs and caffeine-pretreated mice following 6-hydroxydopamine lesioning. Our findings raise the possibility that A₁ or A(₂A) receptors blockade might also confer a disease-modifying benefit of reduced risk of disabling LID, whereas the effect of their combined inactivation is less clear.</description><subject>Adrenergic Agents - toxicity</subject><subject>Animals</subject><subject>Antiparkinson Agents - adverse effects</subject><subject>Caffeine - administration & dosage</subject><subject>Corpus Striatum - drug effects</subject><subject>Disease Models, Animal</subject><subject>Dynorphins - genetics</subject><subject>Dynorphins - metabolism</subject><subject>Dyskinesia, Drug-Induced - etiology</subject><subject>Dyskinesia, Drug-Induced - genetics</subject><subject>Dyskinesia, Drug-Induced - prevention & control</subject><subject>Enkephalins - genetics</subject><subject>Enkephalins - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Levodopa - adverse effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Oxidopamine - toxicity</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - etiology</subject><subject>Parkinson Disease - genetics</subject><subject>Protein Precursors - genetics</subject><subject>Protein Precursors - metabolism</subject><subject>Purinergic P1 Receptor Antagonists - administration & dosage</subject><subject>Receptor, Adenosine A1 - deficiency</subject><subject>Receptor, Adenosine A2A - deficiency</subject><subject>RNA, Messenger - metabolism</subject><subject>Statistics, Nonparametric</subject><subject>Time Factors</subject><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1UMtOwzAQtJAQLYVfqHwDJBI2tvPoMeItVYJD75UTr1WX1I7sViJHeuM3-yW4Ak47Ozu7ox1CphmkGWTF3TptvDTWY0gZRBKqFGazEzLOqpIlBRMwIuchrAGA8xmckRGDilW54GPy_YAdbo2z1GkqFVoXjEVaH_Zf1HlaXx_2-_qGemyx3zofIlK7FgOdJ_xWJMqsBuXd59Cv0A6d7KSN64mxR5GiaggfsQ9GUmOppBunsDs6vUsfB8HZq0CVCSgDXpBTLbuAl391QhZPj4v7l2T-9vx6X8-TPs95okFK3aBsm1boCJjKdRPf0gKQlQXkMitYWZY807oVWAHLWFOJioNSAAL5hEx_z_a7ZoNq2XuzkX5Y_kfCfwDrxWep</recordid><startdate>20110107</startdate><enddate>20110107</enddate><creator>Xiao, Danqing</creator><creator>Cassin, Jared J</creator><creator>Healy, Brian</creator><creator>Burdett, Thomas C</creator><creator>Chen, Jiang-Fan</creator><creator>Fredholm, Bertil B</creator><creator>Schwarzschild, Michael A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20110107</creationdate><title>Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease</title><author>Xiao, Danqing ; Cassin, Jared J ; Healy, Brian ; Burdett, Thomas C ; Chen, Jiang-Fan ; Fredholm, Bertil B ; Schwarzschild, Michael A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p553-f0aafbeacbc4ffbe2d5fb033f40e27605a16277731ffc4e80212b84830dd004e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adrenergic Agents - toxicity</topic><topic>Animals</topic><topic>Antiparkinson Agents - adverse effects</topic><topic>Caffeine - administration & dosage</topic><topic>Corpus Striatum - drug effects</topic><topic>Disease Models, Animal</topic><topic>Dynorphins - genetics</topic><topic>Dynorphins - metabolism</topic><topic>Dyskinesia, Drug-Induced - etiology</topic><topic>Dyskinesia, Drug-Induced - genetics</topic><topic>Dyskinesia, Drug-Induced - prevention & control</topic><topic>Enkephalins - genetics</topic><topic>Enkephalins - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Levodopa - adverse effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Oxidopamine - toxicity</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - etiology</topic><topic>Parkinson Disease - genetics</topic><topic>Protein Precursors - genetics</topic><topic>Protein Precursors - metabolism</topic><topic>Purinergic P1 Receptor Antagonists - administration & dosage</topic><topic>Receptor, Adenosine A1 - deficiency</topic><topic>Receptor, Adenosine A2A - deficiency</topic><topic>RNA, Messenger - metabolism</topic><topic>Statistics, Nonparametric</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Danqing</creatorcontrib><creatorcontrib>Cassin, Jared J</creatorcontrib><creatorcontrib>Healy, Brian</creatorcontrib><creatorcontrib>Burdett, Thomas C</creatorcontrib><creatorcontrib>Chen, Jiang-Fan</creatorcontrib><creatorcontrib>Fredholm, Bertil B</creatorcontrib><creatorcontrib>Schwarzschild, Michael A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Danqing</au><au>Cassin, Jared J</au><au>Healy, Brian</au><au>Burdett, Thomas C</au><au>Chen, Jiang-Fan</au><au>Fredholm, Bertil B</au><au>Schwarzschild, Michael A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2011-01-07</date><risdate>2011</risdate><volume>1367</volume><spage>310</spage><pages>310-</pages><eissn>1872-6240</eissn><abstract>Adenosine A(₂A) receptor antagonism provides a promising approach to developing nondopaminergic therapy for Parkinson's disease (PD). Clinical trials of A(₂A) antagonists have targeted PD patients with L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve parkinsonian symptoms. The role of adenosine in the development of LID is little known, especially regarding its actions via A₁ receptors. We aimed to examine the effects of genetic deletion and pharmacological blockade of A₁ and/or A(₂A) receptors on the development of LID, on the induction of molecular markers of LID including striatal preprodynorphin and preproenkephalin (PPE), and on the integrity of dopaminergic nigrostriatal neurons in hemiparkinsonian mice. Following a unilateral 6-hydroxydopamine lesion A₁, A(₂A) and double A₁-A(₂A) knockout (KO) and wild-type littermate mice, and mice pretreated with caffeine (an antagonist of both A₁ and A(₂A) receptors) or saline were treated daily for 18-21 days with a low dose of L-DOPA. Total abnormal involuntary movements (AIMs, a measure of LID) were significantly attenuated (p<0.05) in A₁ and A(₂A) KOs, but not in A₁-A(₂A) KOs and caffeine-pretreated mice. An elevation of PPE mRNA ipsilateral to the lesion in WT mice was reduced in all KO mice. In addition, neuronal integrity assessed by striatal dopamine content was similar in all KOs and caffeine-pretreated mice following 6-hydroxydopamine lesioning. Our findings raise the possibility that A₁ or A(₂A) receptors blockade might also confer a disease-modifying benefit of reduced risk of disabling LID, whereas the effect of their combined inactivation is less clear.</abstract><cop>Netherlands</cop><pmid>20828543</pmid><doi>10.1016/j.brainres.2010.08.099</doi></addata></record> |
| fulltext | fulltext |
| identifier | EISSN: 1872-6240 |
| ispartof | Brain research, 2011-01, Vol.1367, p.310 |
| issn | 1872-6240 |
| language | eng |
| recordid | cdi_pubmed_primary_20828543 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adrenergic Agents - toxicity Animals Antiparkinson Agents - adverse effects Caffeine - administration & dosage Corpus Striatum - drug effects Disease Models, Animal Dynorphins - genetics Dynorphins - metabolism Dyskinesia, Drug-Induced - etiology Dyskinesia, Drug-Induced - genetics Dyskinesia, Drug-Induced - prevention & control Enkephalins - genetics Enkephalins - metabolism Gene Expression Regulation - drug effects Levodopa - adverse effects Mice Mice, Inbred C57BL Mice, Knockout Oxidopamine - toxicity Parkinson Disease - drug therapy Parkinson Disease - etiology Parkinson Disease - genetics Protein Precursors - genetics Protein Precursors - metabolism Purinergic P1 Receptor Antagonists - administration & dosage Receptor, Adenosine A1 - deficiency Receptor, Adenosine A2A - deficiency RNA, Messenger - metabolism Statistics, Nonparametric Time Factors |
| title | Deletion of adenosine A₁ or A(₂A) receptors reduces L-3,4-dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson's disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T02%3A05%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Deletion%20of%20adenosine%20A%E2%82%81%20or%20A(%E2%82%82A)%20receptors%20reduces%20L-3,4-dihydroxyphenylalanine-induced%20dyskinesia%20in%20a%20model%20of%20Parkinson's%20disease&rft.jtitle=Brain%20research&rft.au=Xiao,%20Danqing&rft.date=2011-01-07&rft.volume=1367&rft.spage=310&rft.pages=310-&rft.eissn=1872-6240&rft_id=info:doi/10.1016/j.brainres.2010.08.099&rft_dat=%3Cpubmed%3E20828543%3C/pubmed%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/20828543&rfr_iscdi=true |