Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism
Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be in...
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| Veröffentlicht in: | Neuro-degenerative diseases 2012-01, Vol.9 (2), p.87-98 |
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| creator | BenMoyal-Segal, Liat Soreq, Lilach Ben-Shaul, Yoram Ben-Ari, Shani Ben-Moshe, Tehila Aviel, Sigal Bergman, Hagai Soreq, Hermona |
| description | Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression. |
| doi_str_mv | 10.1159/000331328 |
| format | Article |
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We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.</description><identifier>ISSN: 1660-2854</identifier><identifier>EISSN: 1660-2862</identifier><identifier>DOI: 10.1159/000331328</identifier><identifier>PMID: 22042332</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Acetylcholinesterase - genetics ; Adaptation, Biological ; Alternative Splicing - genetics ; Animals ; Cluster Analysis ; Environmental Exposure - adverse effects ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Isoenzymes ; Mice ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; Original Paper ; Parkinsonian Disorders - enzymology ; Parkinsonian Disorders - genetics ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins - genetics ; Risk Factors</subject><ispartof>Neuro-degenerative diseases, 2012-01, Vol.9 (2), p.87-98</ispartof><rights>2011 S. Karger AG, Basel</rights><rights>Copyright © 2011 S. Karger AG, Basel.</rights><rights>Copyright (c) 2012 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c333t-c6f02095df0511c1a16512ac76d0cf7e8bdd5b5183c3676fa88f2864236677b43</citedby><cites>FETCH-LOGICAL-c333t-c6f02095df0511c1a16512ac76d0cf7e8bdd5b5183c3676fa88f2864236677b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22042332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BenMoyal-Segal, Liat</creatorcontrib><creatorcontrib>Soreq, Lilach</creatorcontrib><creatorcontrib>Ben-Shaul, Yoram</creatorcontrib><creatorcontrib>Ben-Ari, Shani</creatorcontrib><creatorcontrib>Ben-Moshe, Tehila</creatorcontrib><creatorcontrib>Aviel, Sigal</creatorcontrib><creatorcontrib>Bergman, Hagai</creatorcontrib><creatorcontrib>Soreq, Hermona</creatorcontrib><title>Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism</title><title>Neuro-degenerative diseases</title><addtitle>Neurodegener Dis</addtitle><description>Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.</description><subject>Acetylcholinesterase - genetics</subject><subject>Adaptation, Biological</subject><subject>Alternative Splicing - genetics</subject><subject>Animals</subject><subject>Cluster Analysis</subject><subject>Environmental Exposure - adverse effects</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isoenzymes</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Original Paper</subject><subject>Parkinsonian Disorders - enzymology</subject><subject>Parkinsonian Disorders - genetics</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Recombinant Proteins - genetics</subject><subject>Risk Factors</subject><issn>1660-2854</issn><issn>1660-2862</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><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>eNpd0DtPwzAQB3ALgWh5DOwIRWJADAE_YjsZq6o8pEogoHPkOHZxmzjBTor49hhaMjD5ht_d-f4AnCF4gxDNbiGEhCCC0z0wRozBGKcM7w81TUbgyPsVhDjjGToEI4xhggnBY7CYlKLtzEZFk6pTzorf-rWtjDR2GU0b51QlOuWjT9O9R3PlfTSzG-MaWyvbiSp6MX4dNTp6Fm5trG-s8fUJONCi8up09x6Dxd3sbfoQz5_uH6eTeSwJIV0smYYYZrTUkCIkkUCMIiwkZyWUmqu0KEtaUJQSSRhnWqSpDqeFrzPGeZGQY3C1ndu65qNXvstr46WqKmFV0_s8Q1lGOUU8yMt_ctX04dzK5whiThMedgd1vVXSNd47pfPWmVq4r4Dyn6jzIepgL3YT-6JW5SD_sg3gfAvWwi2VG8Cu_xs9oICA</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>BenMoyal-Segal, Liat</creator><creator>Soreq, Lilach</creator><creator>Ben-Shaul, Yoram</creator><creator>Ben-Ari, Shani</creator><creator>Ben-Moshe, Tehila</creator><creator>Aviel, Sigal</creator><creator>Bergman, Hagai</creator><creator>Soreq, Hermona</creator><general>S. Karger AG</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20120101</creationdate><title>Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism</title><author>BenMoyal-Segal, Liat ; Soreq, Lilach ; Ben-Shaul, Yoram ; Ben-Ari, Shani ; Ben-Moshe, Tehila ; Aviel, Sigal ; Bergman, Hagai ; Soreq, Hermona</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-c6f02095df0511c1a16512ac76d0cf7e8bdd5b5183c3676fa88f2864236677b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acetylcholinesterase - genetics</topic><topic>Adaptation, Biological</topic><topic>Alternative Splicing - genetics</topic><topic>Animals</topic><topic>Cluster Analysis</topic><topic>Environmental Exposure - adverse effects</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Isoenzymes</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Original Paper</topic><topic>Parkinsonian Disorders - enzymology</topic><topic>Parkinsonian Disorders - genetics</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Recombinant Proteins - genetics</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BenMoyal-Segal, Liat</creatorcontrib><creatorcontrib>Soreq, Lilach</creatorcontrib><creatorcontrib>Ben-Shaul, Yoram</creatorcontrib><creatorcontrib>Ben-Ari, Shani</creatorcontrib><creatorcontrib>Ben-Moshe, Tehila</creatorcontrib><creatorcontrib>Aviel, Sigal</creatorcontrib><creatorcontrib>Bergman, Hagai</creatorcontrib><creatorcontrib>Soreq, Hermona</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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 China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Neuro-degenerative diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BenMoyal-Segal, Liat</au><au>Soreq, Lilach</au><au>Ben-Shaul, Yoram</au><au>Ben-Ari, Shani</au><au>Ben-Moshe, Tehila</au><au>Aviel, Sigal</au><au>Bergman, Hagai</au><au>Soreq, Hermona</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism</atitle><jtitle>Neuro-degenerative diseases</jtitle><addtitle>Neurodegener Dis</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>9</volume><issue>2</issue><spage>87</spage><epage>98</epage><pages>87-98</pages><issn>1660-2854</issn><eissn>1660-2862</eissn><abstract>Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain’s capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>22042332</pmid><doi>10.1159/000331328</doi><tpages>12</tpages></addata></record> |
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| subjects | Acetylcholinesterase - genetics Adaptation, Biological Alternative Splicing - genetics Animals Cluster Analysis Environmental Exposure - adverse effects Gene Expression Profiling Humans Immunohistochemistry Isoenzymes Mice Mice, Transgenic Oligonucleotide Array Sequence Analysis Original Paper Parkinsonian Disorders - enzymology Parkinsonian Disorders - genetics Real-Time Polymerase Chain Reaction Recombinant Proteins - genetics Risk Factors |
| title | Adaptive Alternative Splicing Correlates with Less Environmental Risk of Parkinsonism |
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