From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms
The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression...
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| Veröffentlicht in: | Neuropharmacology 2015-10, Vol.97, p.365-375 |
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| creator | Marin, C. Bonastre, M. Mengod, G. Cortés, R. Rodríguez-Oroz, M.C. |
| description | The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bilateral have not been described yet.
We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats.
Sequentially bilateral lesioned animals showed a bilateral increase in striatal preproenkephalin (PPE) mRNA without changes in pre-prodynorphin (PDyn) mRNA expression. The increase in dyskinesias when parkinsonism becomes bilateral was mostly due to an increase in orolingual dyskinesias associated to a increase in PDyn mRNA expression. Right lesion induces, or facilitates when first-done, a greater level of LIDs and an increase in striatal PPE and PDyn mRNAs in the second lesioned side.
We describe a new striatal molecular pattern that appears when parkinsonism becomes bilateral and the relevance of the lateralization for the development of LIDs.
•A new striatal molecular pattern is obtained when parkinsonism becomes sequentially bilateral.•Right nigral lesion induces, or facilitates, a greater level of levodopa-induced dyskinesias.•Orolingual abnormal movements and striatal preprodynorphin (PDyn) mRNA increase when parkinsonism becomes bilateral. |
| doi_str_mv | 10.1016/j.neuropharm.2015.06.004 |
| format | Article |
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We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats.
Sequentially bilateral lesioned animals showed a bilateral increase in striatal preproenkephalin (PPE) mRNA without changes in pre-prodynorphin (PDyn) mRNA expression. The increase in dyskinesias when parkinsonism becomes bilateral was mostly due to an increase in orolingual dyskinesias associated to a increase in PDyn mRNA expression. Right lesion induces, or facilitates when first-done, a greater level of LIDs and an increase in striatal PPE and PDyn mRNAs in the second lesioned side.
We describe a new striatal molecular pattern that appears when parkinsonism becomes bilateral and the relevance of the lateralization for the development of LIDs.
•A new striatal molecular pattern is obtained when parkinsonism becomes sequentially bilateral.•Right nigral lesion induces, or facilitates, a greater level of levodopa-induced dyskinesias.•Orolingual abnormal movements and striatal preprodynorphin (PDyn) mRNA increase when parkinsonism becomes bilateral.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/j.neuropharm.2015.06.004</identifier><identifier>PMID: 26113400</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>6-Hydroxydopamine ; Animals ; Antiparkinson Agents - adverse effects ; Basal ganglia ; Corpus Striatum - metabolism ; Corpus Striatum - pathology ; Dynorphins - metabolism ; Dyskinesia ; Dyskinesia, Drug-Induced - metabolism ; Enkephalins - metabolism ; Functional Laterality - physiology ; Levodopa - adverse effects ; Male ; Motor Activity - physiology ; Oxidopamine ; Parkinson's disease ; Parkinsonian Disorders - metabolism ; Parkinsonian Disorders - pathology ; Preprodynorphin ; Preproenkephalin ; Protein Precursors - metabolism ; Rats, Sprague-Dawley ; RNA, Messenger - metabolism</subject><ispartof>Neuropharmacology, 2015-10, Vol.97, p.365-375</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-1d1e9bd9fb82125cb50423cfd42540dd2339279cf959f736f07ceae8cb7aa1ca3</citedby><cites>FETCH-LOGICAL-c374t-1d1e9bd9fb82125cb50423cfd42540dd2339279cf959f736f07ceae8cb7aa1ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuropharm.2015.06.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26113400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marin, C.</creatorcontrib><creatorcontrib>Bonastre, M.</creatorcontrib><creatorcontrib>Mengod, G.</creatorcontrib><creatorcontrib>Cortés, R.</creatorcontrib><creatorcontrib>Rodríguez-Oroz, M.C.</creatorcontrib><title>From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bilateral have not been described yet.
We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats.
Sequentially bilateral lesioned animals showed a bilateral increase in striatal preproenkephalin (PPE) mRNA without changes in pre-prodynorphin (PDyn) mRNA expression. The increase in dyskinesias when parkinsonism becomes bilateral was mostly due to an increase in orolingual dyskinesias associated to a increase in PDyn mRNA expression. Right lesion induces, or facilitates when first-done, a greater level of LIDs and an increase in striatal PPE and PDyn mRNAs in the second lesioned side.
We describe a new striatal molecular pattern that appears when parkinsonism becomes bilateral and the relevance of the lateralization for the development of LIDs.
•A new striatal molecular pattern is obtained when parkinsonism becomes sequentially bilateral.•Right nigral lesion induces, or facilitates, a greater level of levodopa-induced dyskinesias.•Orolingual abnormal movements and striatal preprodynorphin (PDyn) mRNA increase when parkinsonism becomes bilateral.</description><subject>6-Hydroxydopamine</subject><subject>Animals</subject><subject>Antiparkinson Agents - adverse effects</subject><subject>Basal ganglia</subject><subject>Corpus Striatum - metabolism</subject><subject>Corpus Striatum - pathology</subject><subject>Dynorphins - metabolism</subject><subject>Dyskinesia</subject><subject>Dyskinesia, Drug-Induced - metabolism</subject><subject>Enkephalins - metabolism</subject><subject>Functional Laterality - physiology</subject><subject>Levodopa - adverse effects</subject><subject>Male</subject><subject>Motor Activity - physiology</subject><subject>Oxidopamine</subject><subject>Parkinson's disease</subject><subject>Parkinsonian Disorders - metabolism</subject><subject>Parkinsonian Disorders - pathology</subject><subject>Preprodynorphin</subject><subject>Preproenkephalin</subject><subject>Protein Precursors - metabolism</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - metabolism</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE2LFDEQhoMo7uzqX5AcvXRv5aO_vOmyq8KCFz2HdFJhM3Z3xlS3sv56M8y4HoWCouB5q6iHMS6gFiDa63294JbT4cHmuZYgmhraGkA_YzvRd6rqoNXP2Q5A9pUaoL9gl0R7KEQv-pfsQrZCKA2wY7_ucpr5tsTJrpjtxNfEx6fhYPP3uFBaIs3v-G0I6FbiKfAzEH_bNaaFl_KPVFCkaInbxXNLlFwsmOdzmtBtk818Rvdgj8voFXsR7ET4-tyv2Le72683n6r7Lx8_37y_r5zq9FoJL3AY_RDGXgrZuLEBLZULXstGg_dSqUF2gwtDM4ROtQE6hxZ7N3bWCmfVFXt72nvI6ceGtJo5ksNpsgumjYzoQKtG6kYUtD-hLieijMEccpxtfjQCzFG72Zt_2s1Ru4HWFKkl-uZ8ZRtn9E_Bv54L8OEEYPn1Z8RsyEVcHPqYi1PjU_z_lT_V0Jyh</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Marin, C.</creator><creator>Bonastre, M.</creator><creator>Mengod, G.</creator><creator>Cortés, R.</creator><creator>Rodríguez-Oroz, M.C.</creator><general>Elsevier 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></search><sort><creationdate>20151001</creationdate><title>From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms</title><author>Marin, C. ; Bonastre, M. ; Mengod, G. ; Cortés, R. ; Rodríguez-Oroz, M.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-1d1e9bd9fb82125cb50423cfd42540dd2339279cf959f736f07ceae8cb7aa1ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>6-Hydroxydopamine</topic><topic>Animals</topic><topic>Antiparkinson Agents - adverse effects</topic><topic>Basal ganglia</topic><topic>Corpus Striatum - metabolism</topic><topic>Corpus Striatum - pathology</topic><topic>Dynorphins - metabolism</topic><topic>Dyskinesia</topic><topic>Dyskinesia, Drug-Induced - metabolism</topic><topic>Enkephalins - metabolism</topic><topic>Functional Laterality - physiology</topic><topic>Levodopa - adverse effects</topic><topic>Male</topic><topic>Motor Activity - physiology</topic><topic>Oxidopamine</topic><topic>Parkinson's disease</topic><topic>Parkinsonian Disorders - metabolism</topic><topic>Parkinsonian Disorders - pathology</topic><topic>Preprodynorphin</topic><topic>Preproenkephalin</topic><topic>Protein Precursors - metabolism</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marin, C.</creatorcontrib><creatorcontrib>Bonastre, M.</creatorcontrib><creatorcontrib>Mengod, G.</creatorcontrib><creatorcontrib>Cortés, R.</creatorcontrib><creatorcontrib>Rodríguez-Oroz, M.C.</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><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marin, C.</au><au>Bonastre, M.</au><au>Mengod, G.</au><au>Cortés, R.</au><au>Rodríguez-Oroz, M.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>97</volume><spage>365</spage><epage>375</epage><pages>365-375</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><abstract>The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bilateral have not been described yet.
We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats.
Sequentially bilateral lesioned animals showed a bilateral increase in striatal preproenkephalin (PPE) mRNA without changes in pre-prodynorphin (PDyn) mRNA expression. The increase in dyskinesias when parkinsonism becomes bilateral was mostly due to an increase in orolingual dyskinesias associated to a increase in PDyn mRNA expression. Right lesion induces, or facilitates when first-done, a greater level of LIDs and an increase in striatal PPE and PDyn mRNAs in the second lesioned side.
We describe a new striatal molecular pattern that appears when parkinsonism becomes bilateral and the relevance of the lateralization for the development of LIDs.
•A new striatal molecular pattern is obtained when parkinsonism becomes sequentially bilateral.•Right nigral lesion induces, or facilitates, a greater level of levodopa-induced dyskinesias.•Orolingual abnormal movements and striatal preprodynorphin (PDyn) mRNA increase when parkinsonism becomes bilateral.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26113400</pmid><doi>10.1016/j.neuropharm.2015.06.004</doi><tpages>11</tpages></addata></record> |
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| subjects | 6-Hydroxydopamine Animals Antiparkinson Agents - adverse effects Basal ganglia Corpus Striatum - metabolism Corpus Striatum - pathology Dynorphins - metabolism Dyskinesia Dyskinesia, Drug-Induced - metabolism Enkephalins - metabolism Functional Laterality - physiology Levodopa - adverse effects Male Motor Activity - physiology Oxidopamine Parkinson's disease Parkinsonian Disorders - metabolism Parkinsonian Disorders - pathology Preprodynorphin Preproenkephalin Protein Precursors - metabolism Rats, Sprague-Dawley RNA, Messenger - metabolism |
| title | From unilateral to bilateral parkinsonism: Effects of lateralization on dyskinesias and associated molecular mechanisms |
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