Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system

Abstract Background and aims Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of...

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Veröffentlicht in:Brain research 2015-07, Vol.1614, p.51-59
Hauptverfasser: Böttner, Martina, Fricke, Tobias, Müller, Melanie, Barrenschee, Martina, Deuschl, Günther, Schneider, Susanne A, Egberts, Jan-Hendrik, Becker, Thomas, Fritscher-Ravens, Annette, Ellrichmann, Mark, Schulz-Schaeffer, Walter J, Wedel, Thilo
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container_title Brain research
container_volume 1614
creator Böttner, Martina
Fricke, Tobias
Müller, Melanie
Barrenschee, Martina
Deuschl, Günther
Schneider, Susanne A
Egberts, Jan-Hendrik
Becker, Thomas
Fritscher-Ravens, Annette
Ellrichmann, Mark
Schulz-Schaeffer, Walter J
Wedel, Thilo
description Abstract Background and aims Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus. Material and methods Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin. Results a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS. Conclusions The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.
doi_str_mv 10.1016/j.brainres.2015.04.015
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Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus. Material and methods Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin. Results a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS. Conclusions The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2015.04.015</identifier><identifier>PMID: 25896939</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Age Factors ; Aged ; Alpha synuclein ; alpha-Synuclein - genetics ; alpha-Synuclein - metabolism ; Animals ; Animals, Newborn ; Cells, Cultured ; Enteric nerve cell culture ; Enteric nervous system ; Enteric Nervous System - cytology ; Enteric Nervous System - growth &amp; development ; Enteric Nervous System - metabolism ; Gene Expression Regulation - drug effects ; Glial Cell Line-Derived Neurotrophic Factor - pharmacology ; Human colon ; Humans ; In Vitro Techniques ; Male ; Neurology ; Neurons - cytology ; Neurons - drug effects ; Rats ; RNA, Messenger - metabolism ; Statistics, Nonparametric ; Synaptic vesicles ; Synaptic Vesicles - metabolism ; Synaptophysin - metabolism ; Ubiquitin Thiolesterase - metabolism</subject><ispartof>Brain research, 2015-07, Vol.1614, p.51-59</ispartof><rights>Elsevier B.V.</rights><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-72ab82a2ed1fce066ab3a5e3905fff443f2cb188bb5d33d4daf7973bf25641b83</citedby><cites>FETCH-LOGICAL-c526t-72ab82a2ed1fce066ab3a5e3905fff443f2cb188bb5d33d4daf7973bf25641b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2015.04.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25896939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Böttner, Martina</creatorcontrib><creatorcontrib>Fricke, Tobias</creatorcontrib><creatorcontrib>Müller, Melanie</creatorcontrib><creatorcontrib>Barrenschee, Martina</creatorcontrib><creatorcontrib>Deuschl, Günther</creatorcontrib><creatorcontrib>Schneider, Susanne A</creatorcontrib><creatorcontrib>Egberts, Jan-Hendrik</creatorcontrib><creatorcontrib>Becker, Thomas</creatorcontrib><creatorcontrib>Fritscher-Ravens, Annette</creatorcontrib><creatorcontrib>Ellrichmann, Mark</creatorcontrib><creatorcontrib>Schulz-Schaeffer, Walter J</creatorcontrib><creatorcontrib>Wedel, Thilo</creatorcontrib><title>Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract Background and aims Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus. Material and methods Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin. Results a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS. Conclusions The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. 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Fricke, Tobias ; Müller, Melanie ; Barrenschee, Martina ; Deuschl, Günther ; Schneider, Susanne A ; Egberts, Jan-Hendrik ; Becker, Thomas ; Fritscher-Ravens, Annette ; Ellrichmann, Mark ; Schulz-Schaeffer, Walter J ; Wedel, Thilo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-72ab82a2ed1fce066ab3a5e3905fff443f2cb188bb5d33d4daf7973bf25641b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Age Factors</topic><topic>Aged</topic><topic>Alpha synuclein</topic><topic>alpha-Synuclein - genetics</topic><topic>alpha-Synuclein - metabolism</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Cells, Cultured</topic><topic>Enteric nerve cell culture</topic><topic>Enteric nervous system</topic><topic>Enteric Nervous System - cytology</topic><topic>Enteric Nervous System - growth &amp; development</topic><topic>Enteric Nervous System - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - pharmacology</topic><topic>Human colon</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Neurology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Rats</topic><topic>RNA, Messenger - metabolism</topic><topic>Statistics, Nonparametric</topic><topic>Synaptic vesicles</topic><topic>Synaptic Vesicles - metabolism</topic><topic>Synaptophysin - metabolism</topic><topic>Ubiquitin Thiolesterase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Böttner, Martina</creatorcontrib><creatorcontrib>Fricke, Tobias</creatorcontrib><creatorcontrib>Müller, Melanie</creatorcontrib><creatorcontrib>Barrenschee, Martina</creatorcontrib><creatorcontrib>Deuschl, Günther</creatorcontrib><creatorcontrib>Schneider, Susanne A</creatorcontrib><creatorcontrib>Egberts, Jan-Hendrik</creatorcontrib><creatorcontrib>Becker, Thomas</creatorcontrib><creatorcontrib>Fritscher-Ravens, Annette</creatorcontrib><creatorcontrib>Ellrichmann, Mark</creatorcontrib><creatorcontrib>Schulz-Schaeffer, Walter J</creatorcontrib><creatorcontrib>Wedel, Thilo</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>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Böttner, Martina</au><au>Fricke, Tobias</au><au>Müller, Melanie</au><au>Barrenschee, Martina</au><au>Deuschl, Günther</au><au>Schneider, Susanne A</au><au>Egberts, Jan-Hendrik</au><au>Becker, Thomas</au><au>Fritscher-Ravens, Annette</au><au>Ellrichmann, Mark</au><au>Schulz-Schaeffer, Walter J</au><au>Wedel, Thilo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2015-07-21</date><risdate>2015</risdate><volume>1614</volume><spage>51</spage><epage>59</epage><pages>51-59</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>Abstract Background and aims Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus. Material and methods Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin. Results a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS. Conclusions The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25896939</pmid><doi>10.1016/j.brainres.2015.04.015</doi><tpages>9</tpages></addata></record>
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subjects Age Factors
Aged
Alpha synuclein
alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Animals
Animals, Newborn
Cells, Cultured
Enteric nerve cell culture
Enteric nervous system
Enteric Nervous System - cytology
Enteric Nervous System - growth & development
Enteric Nervous System - metabolism
Gene Expression Regulation - drug effects
Glial Cell Line-Derived Neurotrophic Factor - pharmacology
Human colon
Humans
In Vitro Techniques
Male
Neurology
Neurons - cytology
Neurons - drug effects
Rats
RNA, Messenger - metabolism
Statistics, Nonparametric
Synaptic vesicles
Synaptic Vesicles - metabolism
Synaptophysin - metabolism
Ubiquitin Thiolesterase - metabolism
title Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system
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