Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system
Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration 1 , 2 . The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) 3 , 4 is permeable to Na + and Ca 2+ , and excessive accumulation of these ions is associated with axonal degeneration 5 . We tested...
Gespeichert in:
| Veröffentlicht in: | Nature medicine 2007-12, Vol.13 (12), p.1483-1489 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1489 |
|---|---|
| container_issue | 12 |
| container_start_page | 1483 |
| container_title | Nature medicine |
| container_volume | 13 |
| creator | Friese, Manuel A Craner, Matthew J Etzensperger, Ruth Vergo, Sandra Wemmie, John A Welsh, Michael J Vincent, Angela Fugger, Lars |
| description | Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration
1
,
2
. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1)
3
,
4
is permeable to Na
+
and Ca
2+
, and excessive accumulation of these ions is associated with axonal degeneration
5
. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After induction of experimental autoimmune encephalomyelitis (EAE),
Asic1
−/−
mice showed both a markedly reduced clinical deficit and reduced axonal degeneration compared to wild-type mice. Consistently with acidosis-mediated injury, pH measurements in the spinal cord of EAE mice showed tissue acidosis sufficient to open ASIC1. The acidosis-related protective effect of
Asic1
disruption was also observed in nerve explants
in vitro
. Amiloride, a licensed and clinically safe blocker of ASICs, was equally neuroprotective in nerve explants and in EAE. Although ASICs are also expressed by immune cells, this expression is unlikely to explain the neuroprotective effect of
Asic1
inactivation, as CNS inflammation was similar in wild-type and
Asic1
−/−
mice. In addition, adoptive transfer of T cells from wild-type mice did not affect the protection mediated by
Asic1
disruption. These results suggest that ASIC1 blockers could provide neuroprotection in multiple sclerosis. |
| doi_str_mv | 10.1038/nm1668 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_762269358</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A192447397</galeid><sourcerecordid>A192447397</sourcerecordid><originalsourceid>FETCH-LOGICAL-c641t-6580f74bbd30703dd2900b9eaed4a1c9fb674f2efeebd4581133acdbb82eade73</originalsourceid><addsrcrecordid>eNqNkt9r3SAUx8PYWLtu-xOG7KGjD-k0Go2Pl9JthUJhv9hbMHpyr8VoF01p__sZcuG25bINH_R4Pt-Dfs8pircEnxJMm49-IJw3z4pDUjNeEoF_Pc9nLJqykTU_KF7FeI0xpriWL4sDIqRkBJPD4nalrSkj-Gj9Gtngkd4o78GVBOng02i7KUFEKSB1F7xyyMAaPIwqzbD1SE0p2GGYPOSod2oYllToUdoA0pCLZFmW3IYpongfEwyvixe9chHebPej4sen8-9nX8rLq88XZ6vLUnNGUsnrBveCdZ2hWGBqTCUx7iQoMEwRLfuOC9ZX0AN0htUNIZQqbbquqUAZEPSo-LDUvRnD7wliagcbNTinPOTXtIJXFZe0bjJ5_FeSS8xEJeU_wQqzRvC6zuD7J-B1mMZsYWYqSghrMM9QuUBr5aDNBobsll4cdsFDb_P1isiKMUHl_KHTPXxeBgar9wpOHgnmpsJdWqspxvbi29f_Z69-PmaPH7AbUC5tYnDT3Pu4F9RjiHGEvr0Z7aDG-5bgdp7ddpndDL7b-jV1A5gdth3WXTNjTvk1jDtDn5T6A_Q69Oo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>223114806</pqid></control><display><type>article</type><title>Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system</title><source>MEDLINE</source><source>Nature</source><source>Springer Nature - Complete Springer Journals</source><creator>Friese, Manuel A ; Craner, Matthew J ; Etzensperger, Ruth ; Vergo, Sandra ; Wemmie, John A ; Welsh, Michael J ; Vincent, Angela ; Fugger, Lars</creator><creatorcontrib>Friese, Manuel A ; Craner, Matthew J ; Etzensperger, Ruth ; Vergo, Sandra ; Wemmie, John A ; Welsh, Michael J ; Vincent, Angela ; Fugger, Lars</creatorcontrib><description>Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration
1
,
2
. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1)
3
,
4
is permeable to Na
+
and Ca
2+
, and excessive accumulation of these ions is associated with axonal degeneration
5
. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After induction of experimental autoimmune encephalomyelitis (EAE),
Asic1
−/−
mice showed both a markedly reduced clinical deficit and reduced axonal degeneration compared to wild-type mice. Consistently with acidosis-mediated injury, pH measurements in the spinal cord of EAE mice showed tissue acidosis sufficient to open ASIC1. The acidosis-related protective effect of
Asic1
disruption was also observed in nerve explants
in vitro
. Amiloride, a licensed and clinically safe blocker of ASICs, was equally neuroprotective in nerve explants and in EAE. Although ASICs are also expressed by immune cells, this expression is unlikely to explain the neuroprotective effect of
Asic1
inactivation, as CNS inflammation was similar in wild-type and
Asic1
−/−
mice. In addition, adoptive transfer of T cells from wild-type mice did not affect the protection mediated by
Asic1
disruption. These results suggest that ASIC1 blockers could provide neuroprotection in multiple sclerosis.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm1668</identifier><identifier>PMID: 17994101</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Acid Sensing Ion Channels ; Acids ; Amiloride - pharmacology ; Animals ; Autoimmune diseases ; Autoimmunity ; Axons - pathology ; Biomedical and Life Sciences ; Biomedical research ; Biomedicine ; Calcium ; Cancer Research ; Central nervous system ; Central Nervous System - immunology ; Central Nervous System - pathology ; Encephalomyelitis, Autoimmune, Experimental - genetics ; Encephalomyelitis, Autoimmune, Experimental - metabolism ; Inactivation ; Infectious Diseases ; Inflammation - pathology ; Ions ; Lesions ; letter ; Membrane Proteins - metabolism ; Membrane Proteins - physiology ; Metabolic Diseases ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Medicine ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Multiple Sclerosis - metabolism ; Nerve Degeneration ; Nerve Tissue Proteins - metabolism ; Nerve Tissue Proteins - physiology ; Neurology ; Neuroprotective Agents - pharmacology ; Neurosciences ; Rodents ; Sodium ; Sodium Channels - metabolism ; Sodium Channels - physiology ; Spinal Cord - pathology</subject><ispartof>Nature medicine, 2007-12, Vol.13 (12), p.1483-1489</ispartof><rights>Springer Nature America, Inc. 2007</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-6580f74bbd30703dd2900b9eaed4a1c9fb674f2efeebd4581133acdbb82eade73</citedby><cites>FETCH-LOGICAL-c641t-6580f74bbd30703dd2900b9eaed4a1c9fb674f2efeebd4581133acdbb82eade73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nm1668$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm1668$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17994101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Friese, Manuel A</creatorcontrib><creatorcontrib>Craner, Matthew J</creatorcontrib><creatorcontrib>Etzensperger, Ruth</creatorcontrib><creatorcontrib>Vergo, Sandra</creatorcontrib><creatorcontrib>Wemmie, John A</creatorcontrib><creatorcontrib>Welsh, Michael J</creatorcontrib><creatorcontrib>Vincent, Angela</creatorcontrib><creatorcontrib>Fugger, Lars</creatorcontrib><title>Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration
1
,
2
. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1)
3
,
4
is permeable to Na
+
and Ca
2+
, and excessive accumulation of these ions is associated with axonal degeneration
5
. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After induction of experimental autoimmune encephalomyelitis (EAE),
Asic1
−/−
mice showed both a markedly reduced clinical deficit and reduced axonal degeneration compared to wild-type mice. Consistently with acidosis-mediated injury, pH measurements in the spinal cord of EAE mice showed tissue acidosis sufficient to open ASIC1. The acidosis-related protective effect of
Asic1
disruption was also observed in nerve explants
in vitro
. Amiloride, a licensed and clinically safe blocker of ASICs, was equally neuroprotective in nerve explants and in EAE. Although ASICs are also expressed by immune cells, this expression is unlikely to explain the neuroprotective effect of
Asic1
inactivation, as CNS inflammation was similar in wild-type and
Asic1
−/−
mice. In addition, adoptive transfer of T cells from wild-type mice did not affect the protection mediated by
Asic1
disruption. These results suggest that ASIC1 blockers could provide neuroprotection in multiple sclerosis.</description><subject>Acid Sensing Ion Channels</subject><subject>Acids</subject><subject>Amiloride - pharmacology</subject><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Axons - pathology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical research</subject><subject>Biomedicine</subject><subject>Calcium</subject><subject>Cancer Research</subject><subject>Central nervous system</subject><subject>Central Nervous System - immunology</subject><subject>Central Nervous System - pathology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - genetics</subject><subject>Encephalomyelitis, Autoimmune, Experimental - metabolism</subject><subject>Inactivation</subject><subject>Infectious Diseases</subject><subject>Inflammation - pathology</subject><subject>Ions</subject><subject>Lesions</subject><subject>letter</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - physiology</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular Medicine</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis - metabolism</subject><subject>Nerve Degeneration</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Neurology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurosciences</subject><subject>Rodents</subject><subject>Sodium</subject><subject>Sodium Channels - metabolism</subject><subject>Sodium Channels - physiology</subject><subject>Spinal Cord - pathology</subject><issn>1078-8956</issn><issn>1546-170X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkt9r3SAUx8PYWLtu-xOG7KGjD-k0Go2Pl9JthUJhv9hbMHpyr8VoF01p__sZcuG25bINH_R4Pt-Dfs8pircEnxJMm49-IJw3z4pDUjNeEoF_Pc9nLJqykTU_KF7FeI0xpriWL4sDIqRkBJPD4nalrSkj-Gj9Gtngkd4o78GVBOng02i7KUFEKSB1F7xyyMAaPIwqzbD1SE0p2GGYPOSod2oYllToUdoA0pCLZFmW3IYpongfEwyvixe9chHebPej4sen8-9nX8rLq88XZ6vLUnNGUsnrBveCdZ2hWGBqTCUx7iQoMEwRLfuOC9ZX0AN0htUNIZQqbbquqUAZEPSo-LDUvRnD7wliagcbNTinPOTXtIJXFZe0bjJ5_FeSS8xEJeU_wQqzRvC6zuD7J-B1mMZsYWYqSghrMM9QuUBr5aDNBobsll4cdsFDb_P1isiKMUHl_KHTPXxeBgar9wpOHgnmpsJdWqspxvbi29f_Z69-PmaPH7AbUC5tYnDT3Pu4F9RjiHGEvr0Z7aDG-5bgdp7ddpndDL7b-jV1A5gdth3WXTNjTvk1jDtDn5T6A_Q69Oo</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Friese, Manuel A</creator><creator>Craner, Matthew J</creator><creator>Etzensperger, Ruth</creator><creator>Vergo, Sandra</creator><creator>Wemmie, John A</creator><creator>Welsh, Michael J</creator><creator>Vincent, Angela</creator><creator>Fugger, Lars</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071201</creationdate><title>Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system</title><author>Friese, Manuel A ; Craner, Matthew J ; Etzensperger, Ruth ; Vergo, Sandra ; Wemmie, John A ; Welsh, Michael J ; Vincent, Angela ; Fugger, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-6580f74bbd30703dd2900b9eaed4a1c9fb674f2efeebd4581133acdbb82eade73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acid Sensing Ion Channels</topic><topic>Acids</topic><topic>Amiloride - pharmacology</topic><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Axons - pathology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical research</topic><topic>Biomedicine</topic><topic>Calcium</topic><topic>Cancer Research</topic><topic>Central nervous system</topic><topic>Central Nervous System - immunology</topic><topic>Central Nervous System - pathology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - genetics</topic><topic>Encephalomyelitis, Autoimmune, Experimental - metabolism</topic><topic>Inactivation</topic><topic>Infectious Diseases</topic><topic>Inflammation - pathology</topic><topic>Ions</topic><topic>Lesions</topic><topic>letter</topic><topic>Membrane Proteins - metabolism</topic><topic>Membrane Proteins - physiology</topic><topic>Metabolic Diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Molecular Medicine</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - genetics</topic><topic>Multiple Sclerosis - metabolism</topic><topic>Nerve Degeneration</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Neurology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neurosciences</topic><topic>Rodents</topic><topic>Sodium</topic><topic>Sodium Channels - metabolism</topic><topic>Sodium Channels - physiology</topic><topic>Spinal Cord - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Friese, Manuel A</creatorcontrib><creatorcontrib>Craner, Matthew J</creatorcontrib><creatorcontrib>Etzensperger, Ruth</creatorcontrib><creatorcontrib>Vergo, Sandra</creatorcontrib><creatorcontrib>Wemmie, John A</creatorcontrib><creatorcontrib>Welsh, Michael J</creatorcontrib><creatorcontrib>Vincent, Angela</creatorcontrib><creatorcontrib>Fugger, Lars</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</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 Pharma Collection</collection><collection>Technology Research Database</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>Research Library (Alumni Edition)</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</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</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>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Friese, Manuel A</au><au>Craner, Matthew J</au><au>Etzensperger, Ruth</au><au>Vergo, Sandra</au><au>Wemmie, John A</au><au>Welsh, Michael J</au><au>Vincent, Angela</au><au>Fugger, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>13</volume><issue>12</issue><spage>1483</spage><epage>1489</epage><pages>1483-1489</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Multiple sclerosis is a neuroinflammatory disease associated with axonal degeneration
1
,
2
. The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1)
3
,
4
is permeable to Na
+
and Ca
2+
, and excessive accumulation of these ions is associated with axonal degeneration
5
. We tested the hypothesis that ASIC1 contributes to axonal degeneration in inflammatory lesions of the central nervous system (CNS). After induction of experimental autoimmune encephalomyelitis (EAE),
Asic1
−/−
mice showed both a markedly reduced clinical deficit and reduced axonal degeneration compared to wild-type mice. Consistently with acidosis-mediated injury, pH measurements in the spinal cord of EAE mice showed tissue acidosis sufficient to open ASIC1. The acidosis-related protective effect of
Asic1
disruption was also observed in nerve explants
in vitro
. Amiloride, a licensed and clinically safe blocker of ASICs, was equally neuroprotective in nerve explants and in EAE. Although ASICs are also expressed by immune cells, this expression is unlikely to explain the neuroprotective effect of
Asic1
inactivation, as CNS inflammation was similar in wild-type and
Asic1
−/−
mice. In addition, adoptive transfer of T cells from wild-type mice did not affect the protection mediated by
Asic1
disruption. These results suggest that ASIC1 blockers could provide neuroprotection in multiple sclerosis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>17994101</pmid><doi>10.1038/nm1668</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-8956 |
| ispartof | Nature medicine, 2007-12, Vol.13 (12), p.1483-1489 |
| issn | 1078-8956 1546-170X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_762269358 |
| source | MEDLINE; Nature; Springer Nature - Complete Springer Journals |
| subjects | Acid Sensing Ion Channels Acids Amiloride - pharmacology Animals Autoimmune diseases Autoimmunity Axons - pathology Biomedical and Life Sciences Biomedical research Biomedicine Calcium Cancer Research Central nervous system Central Nervous System - immunology Central Nervous System - pathology Encephalomyelitis, Autoimmune, Experimental - genetics Encephalomyelitis, Autoimmune, Experimental - metabolism Inactivation Infectious Diseases Inflammation - pathology Ions Lesions letter Membrane Proteins - metabolism Membrane Proteins - physiology Metabolic Diseases Mice Mice, Inbred C57BL Mice, Transgenic Molecular Medicine Multiple sclerosis Multiple Sclerosis - genetics Multiple Sclerosis - metabolism Nerve Degeneration Nerve Tissue Proteins - metabolism Nerve Tissue Proteins - physiology Neurology Neuroprotective Agents - pharmacology Neurosciences Rodents Sodium Sodium Channels - metabolism Sodium Channels - physiology Spinal Cord - pathology |
| title | Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T06%3A16%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Acid-sensing%20ion%20channel-1%20contributes%20to%20axonal%20degeneration%20in%20autoimmune%20inflammation%20of%20the%20central%20nervous%20system&rft.jtitle=Nature%20medicine&rft.au=Friese,%20Manuel%20A&rft.date=2007-12-01&rft.volume=13&rft.issue=12&rft.spage=1483&rft.epage=1489&rft.pages=1483-1489&rft.issn=1078-8956&rft.eissn=1546-170X&rft_id=info:doi/10.1038/nm1668&rft_dat=%3Cgale_proqu%3EA192447397%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=223114806&rft_id=info:pmid/17994101&rft_galeid=A192447397&rfr_iscdi=true |