The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons
6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-med...
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| creator | Lu, Xi Kim-Han, Jeong Sook Harmon, Steve Sakiyama-Elbert, Shelly E O'Malley, Karen L |
| description | 6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment. |
| doi_str_mv | 10.1186/1750-1326-9-17 |
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To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment.</description><identifier>ISSN: 1750-1326</identifier><identifier>EISSN: 1750-1326</identifier><identifier>DOI: 10.1186/1750-1326-9-17</identifier><identifier>PMID: 24885281</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adrenergic Agents - toxicity ; Analysis ; Animals ; Apoptosis ; Autophagy ; Axonal Transport - drug effects ; Axonal Transport - physiology ; Benzoic acid ; Cell death ; Complications and side effects ; Cysteine ; Design of experiments ; Disease Models, Animal ; Dopaminergic Neurons - drug effects ; Dopaminergic Neurons - metabolism ; Fluorescence ; Genetic aspects ; Laboratory animals ; Mice ; Mice, Transgenic ; Microscopy, Confocal ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mutation ; Nerve Degeneration - chemically induced ; Nerve Degeneration - metabolism ; Nerve Degeneration - pathology ; Neurosciences ; Oxidopamine - toxicity ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Physiological aspects ; Proteins ; Rodents</subject><ispartof>Molecular neurodegeneration, 2014-05, Vol.9 (1), p.17-17, Article 17</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Lu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Lu et al.; licensee BioMed Central Ltd. 2014 Lu et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b642t-b4d393f5a1cce381bb1c86ec4155110f24ebed584b3b5c37cb01df9e4ad661273</citedby><cites>FETCH-LOGICAL-b642t-b4d393f5a1cce381bb1c86ec4155110f24ebed584b3b5c37cb01df9e4ad661273</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/PMC4016665/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016665/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24885281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Xi</creatorcontrib><creatorcontrib>Kim-Han, Jeong Sook</creatorcontrib><creatorcontrib>Harmon, Steve</creatorcontrib><creatorcontrib>Sakiyama-Elbert, Shelly E</creatorcontrib><creatorcontrib>O'Malley, Karen L</creatorcontrib><title>The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons</title><title>Molecular neurodegeneration</title><addtitle>Mol Neurodegener</addtitle><description>6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment.</description><subject>Adrenergic Agents - toxicity</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Axonal Transport - drug effects</subject><subject>Axonal Transport - physiology</subject><subject>Benzoic acid</subject><subject>Cell death</subject><subject>Complications and side effects</subject><subject>Cysteine</subject><subject>Design of experiments</subject><subject>Disease Models, Animal</subject><subject>Dopaminergic Neurons - drug effects</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Fluorescence</subject><subject>Genetic aspects</subject><subject>Laboratory animals</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Confocal</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mutation</subject><subject>Nerve Degeneration - chemically induced</subject><subject>Nerve Degeneration - metabolism</subject><subject>Nerve Degeneration - pathology</subject><subject>Neurosciences</subject><subject>Oxidopamine - toxicity</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson Disease - pathology</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Rodents</subject><issn>1750-1326</issn><issn>1750-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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><recordid>eNp1kk1v1DAQhiMEoqVw5YgiceHQFI-_klyQVuWjSJXaQzlbtjPZusR2sLMI_j3etiwtFPng0czj1zOvpqpeAjkC6ORbaAVpgFHZ9A20j6r9XeLxnXivepbzFSG8JUQ8rfYo7zpBO9ivzi8usT7X6asLOQanQ-2dx8XZw1o2ZyfvV4e187N2Kdf6Rwx6qpekQ55jWmoX6iHO2ruAae3sNZCfV09GPWV8cXsfVF8-frg4PmlOzz59Pl6dNkZyujSGD6xno9BgLbIOjAHbSbQchAAgI-VocBAdN8wIy1prCAxjj1wPUgJt2UH17kZ33hiPg8VQGpvUnJzX6aeK2qn7leAu1Tp-V5yAlFIUgdWNgHHxPwL3KzZ6tXVUbR1VfYmLxpvbJlL8tsG8KO-yxWnSAeMmKxC07xmXkhX09V_oVdykYug1RXvZU5B_qLWeULkwxvK13YqqleBECiI4LdTRA1Q5A3pnY8DRlfxDD2yKOSccd2NCGafs0b-Dvbrr7g7_vTjsF6xfwfI</recordid><startdate>20140503</startdate><enddate>20140503</enddate><creator>Lu, Xi</creator><creator>Kim-Han, Jeong Sook</creator><creator>Harmon, Steve</creator><creator>Sakiyama-Elbert, Shelly E</creator><creator>O'Malley, Karen L</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20140503</creationdate><title>The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons</title><author>Lu, Xi ; Kim-Han, Jeong Sook ; Harmon, Steve ; Sakiyama-Elbert, Shelly E ; O'Malley, Karen L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b642t-b4d393f5a1cce381bb1c86ec4155110f24ebed584b3b5c37cb01df9e4ad661273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adrenergic Agents - toxicity</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Axonal Transport - drug effects</topic><topic>Axonal Transport - physiology</topic><topic>Benzoic acid</topic><topic>Cell death</topic><topic>Complications and side effects</topic><topic>Cysteine</topic><topic>Design of experiments</topic><topic>Disease Models, Animal</topic><topic>Dopaminergic Neurons - drug effects</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Fluorescence</topic><topic>Genetic aspects</topic><topic>Laboratory animals</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Confocal</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mutation</topic><topic>Nerve Degeneration - chemically induced</topic><topic>Nerve Degeneration - metabolism</topic><topic>Nerve Degeneration - pathology</topic><topic>Neurosciences</topic><topic>Oxidopamine - toxicity</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - pathology</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Xi</creatorcontrib><creatorcontrib>Kim-Han, Jeong Sook</creatorcontrib><creatorcontrib>Harmon, Steve</creatorcontrib><creatorcontrib>Sakiyama-Elbert, Shelly E</creatorcontrib><creatorcontrib>O'Malley, Karen L</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>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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 China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular neurodegeneration</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Xi</au><au>Kim-Han, Jeong Sook</au><au>Harmon, Steve</au><au>Sakiyama-Elbert, Shelly E</au><au>O'Malley, Karen L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons</atitle><jtitle>Molecular neurodegeneration</jtitle><addtitle>Mol Neurodegener</addtitle><date>2014-05-03</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>17</spage><epage>17</epage><pages>17-17</pages><artnum>17</artnum><issn>1750-1326</issn><eissn>1750-1326</eissn><abstract>6-hydroxydopamine (6-OHDA) is one of the most commonly used toxins for modeling degeneration of dopaminergic (DA) neurons in Parkinson's disease. 6-OHDA also causes axonal degeneration, a process that appears to precede the death of DA neurons. To understand the processes involved in 6-OHDA-mediated axonal degeneration, a microdevice designed to isolate axons fluidically from cell bodies was used in conjunction with green fluorescent protein (GFP)-labeled DA neurons. Results showed that 6-OHDA quickly induced mitochondrial transport dysfunction in both DA and non-DA axons. This appeared to be a general effect on transport function since 6-OHDA also disrupted transport of synaptophysin-tagged vesicles. The effects of 6-OHDA on mitochondrial transport were blocked by the addition of the SOD1-mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), as well as the anti-oxidant N-acetyl-cysteine (NAC) suggesting that free radical species played a role in this process. Temporally, microtubule disruption and autophagy occurred after transport dysfunction yet before DA cell death following 6-OHDA treatment. The results from the study suggest that ROS-mediated transport dysfunction occurs early and plays a significant role in inducing axonal degeneration in response to 6-OHDA treatment.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24885281</pmid><doi>10.1186/1750-1326-9-17</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic Agents - toxicity Analysis Animals Apoptosis Autophagy Axonal Transport - drug effects Axonal Transport - physiology Benzoic acid Cell death Complications and side effects Cysteine Design of experiments Disease Models, Animal Dopaminergic Neurons - drug effects Dopaminergic Neurons - metabolism Fluorescence Genetic aspects Laboratory animals Mice Mice, Transgenic Microscopy, Confocal Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mutation Nerve Degeneration - chemically induced Nerve Degeneration - metabolism Nerve Degeneration - pathology Neurosciences Oxidopamine - toxicity Parkinson Disease - metabolism Parkinson Disease - pathology Physiological aspects Proteins Rodents |
| title | The Parkinsonian mimetic, 6-OHDA, impairs axonal transport in dopaminergic axons |
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