Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors
As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in P...
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| Veröffentlicht in: | Scientific reports 2020-09, Vol.10 (1), p.14426, Article 14426 |
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| creator | Jones-Tabah, Jace Mohammad, Hanan Hadj-Youssef, Shadi Kim, Lucy E. H. Martin, Ryan D. Benaliouad, Faïza Tanny, Jason C. Clarke, Paul B. S. Hébert, Terence E. |
| description | As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson’s disease (PD), alterations in this pathway lead to functional upregulation of extracellular regulated kinases 1/2 (ERK1/2), contributing to
l
-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with
l
-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia. |
| doi_str_mv | 10.1038/s41598-020-71121-8 |
| format | Article |
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l
-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with
l
-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-71121-8</identifier><identifier>PMID: 32879346</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/436 ; 631/154/436/2387 ; 631/378/1689 ; 631/378/1689/1718 ; 631/378/340 ; Amino acid sequence ; Animals ; Biosensing Techniques - methods ; Biosensors ; Cattle industry ; Cell adhesion ; Cell adhesion & migration ; Cells, Cultured ; Confocal microscopy ; Corpus Striatum - cytology ; Corpus Striatum - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Energy transfer ; Enzymatic activity ; Enzyme-linked immunosorbent assay ; Enzymes ; Fibronectin ; Flow cytometry ; Fluorescence Resonance Energy Transfer - methods ; Humanities and Social Sciences ; Hydrogen peroxide ; Levodopa ; Male ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; multidisciplinary ; Mycoplasma bovis ; NAD ; NADH ; NADH oxidase ; Neurons - metabolism ; Nox protein ; Parkinson Disease - metabolism ; Parkinson's disease ; Phages ; Protein folding ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D1 - metabolism ; Science ; Science (multidisciplinary) ; Signal Transduction</subject><ispartof>Scientific reports, 2020-09, Vol.10 (1), p.14426, Article 14426</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-dee7b055a6da2f93b9c9498e76dcb0ac8d959fd90d059bb5638e160c5e2a68523</citedby><cites>FETCH-LOGICAL-c511t-dee7b055a6da2f93b9c9498e76dcb0ac8d959fd90d059bb5638e160c5e2a68523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468292/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468292/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32879346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jones-Tabah, Jace</creatorcontrib><creatorcontrib>Mohammad, Hanan</creatorcontrib><creatorcontrib>Hadj-Youssef, Shadi</creatorcontrib><creatorcontrib>Kim, Lucy E. H.</creatorcontrib><creatorcontrib>Martin, Ryan D.</creatorcontrib><creatorcontrib>Benaliouad, Faïza</creatorcontrib><creatorcontrib>Tanny, Jason C.</creatorcontrib><creatorcontrib>Clarke, Paul B. S.</creatorcontrib><creatorcontrib>Hébert, Terence E.</creatorcontrib><title>Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson’s disease (PD), alterations in this pathway lead to functional upregulation of extracellular regulated kinases 1/2 (ERK1/2), contributing to
l
-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with
l
-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.</description><subject>631/154/436</subject><subject>631/154/436/2387</subject><subject>631/378/1689</subject><subject>631/378/1689/1718</subject><subject>631/378/340</subject><subject>Amino acid sequence</subject><subject>Animals</subject><subject>Biosensing Techniques - methods</subject><subject>Biosensors</subject><subject>Cattle industry</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cells, Cultured</subject><subject>Confocal microscopy</subject><subject>Corpus Striatum - cytology</subject><subject>Corpus Striatum - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Energy transfer</subject><subject>Enzymatic activity</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Fibronectin</subject><subject>Flow cytometry</subject><subject>Fluorescence Resonance Energy Transfer - methods</subject><subject>Humanities and Social Sciences</subject><subject>Hydrogen peroxide</subject><subject>Levodopa</subject><subject>Male</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>multidisciplinary</subject><subject>Mycoplasma bovis</subject><subject>NAD</subject><subject>NADH</subject><subject>NADH oxidase</subject><subject>Neurons - metabolism</subject><subject>Nox protein</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson's disease</subject><subject>Phages</subject><subject>Protein folding</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp1kctqHDEQRUVwiI3jH8giCLzuWI9Wt7QxGD8DhoTgrIUe1WM5PVJb6jGev4_G45jxIrWpgjr3ltBF6Asl3yjh8qS0VCjZEEaanlJGG_kBHTDSioZxxvZ25n10VMoDqSWYaqn6hPY5k73ibXeAni_SZJYhAr6gOIODaU4Zl7CIZhxDXOAQsV-XP5WYg8M_Ta5jSTGYiLOZS9U8gRnBY7vGQ7CQ8XSf5rSEOa_xqmwsrn5d3jXWlA0UUoGqz-Uz-jiYscDRaz9Ev68u785vmtsf19_Pz24bJyidGw_QWyKE6bxhg-JWOdUqCX3nnSXGSa-EGrwinghlrei4BNoRJ4CZTgrGD9Hp1nda2SV4B3HOZtRTDkuT1zqZoN9vYrjXi_Sk-7aTTG0Mjl8NcnpcQZn1Q1rl-j1FUym7itCeV4ptKZdTKRmGtwuU6E1gehuYroHpl8C0rKKvu297k_yLpwJ8C5S6igvIO7f_b_sXEoWkDg</recordid><startdate>20200902</startdate><enddate>20200902</enddate><creator>Jones-Tabah, Jace</creator><creator>Mohammad, Hanan</creator><creator>Hadj-Youssef, Shadi</creator><creator>Kim, Lucy E. 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S.</creatorcontrib><creatorcontrib>Hébert, Terence E.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 One Sustainability</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>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones-Tabah, Jace</au><au>Mohammad, Hanan</au><au>Hadj-Youssef, Shadi</au><au>Kim, Lucy E. H.</au><au>Martin, Ryan D.</au><au>Benaliouad, Faïza</au><au>Tanny, Jason C.</au><au>Clarke, Paul B. S.</au><au>Hébert, Terence E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-09-02</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>14426</spage><pages>14426-</pages><artnum>14426</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson’s disease (PD), alterations in this pathway lead to functional upregulation of extracellular regulated kinases 1/2 (ERK1/2), contributing to
l
-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with
l
-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32879346</pmid><doi>10.1038/s41598-020-71121-8</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/154/436 631/154/436/2387 631/378/1689 631/378/1689/1718 631/378/340 Amino acid sequence Animals Biosensing Techniques - methods Biosensors Cattle industry Cell adhesion Cell adhesion & migration Cells, Cultured Confocal microscopy Corpus Striatum - cytology Corpus Striatum - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Energy transfer Enzymatic activity Enzyme-linked immunosorbent assay Enzymes Fibronectin Flow cytometry Fluorescence Resonance Energy Transfer - methods Humanities and Social Sciences Hydrogen peroxide Levodopa Male Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism multidisciplinary Mycoplasma bovis NAD NADH NADH oxidase Neurons - metabolism Nox protein Parkinson Disease - metabolism Parkinson's disease Phages Protein folding Rats Rats, Sprague-Dawley Receptors, Dopamine D1 - metabolism Science Science (multidisciplinary) Signal Transduction |
| title | Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors |
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