Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production
Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead...
Gespeichert in:
| Veröffentlicht in: | Glia 2013-09, Vol.61 (9), p.1418-1428 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1428 |
|---|---|
| container_issue | 9 |
| container_start_page | 1418 |
| container_title | Glia |
| container_volume | 61 |
| creator | McGivern, Jered V. Patitucci, Teresa N. Nord, Joshua A. Barabas, Marie-Elizabeth A. Stucky, Cheryl L. Ebert, Allison D. |
| description | Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMAΔ7 mouse spinal cord and from SMA‐induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis‐regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology. |
| doi_str_mv | 10.1002/glia.22522 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3941074</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3028560771</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5852-e61a4f8e225f2ea524120e0736b76db74b8361a40650b14ea8d5612878d549ac3</originalsourceid><addsrcrecordid>eNqNkU9v1DAQxS0EokvhwgdAlrggpBT_jZMLUlXBttIKDgX1aE0cZ9etEwc7od1vj7fbroAD4jQe-_eeZvwQek3JCSWEfVh7ByeMScaeoAUldVVQysunaEGqWhRU1PQIvUjpmhCaG_UcHTFe8bqW5QLdXI5uAI_7OZnZQ8QwxTButhhSPpjtZBO2dxvXuAlDM4TYZ9iAN27ucbTrrJlcGDAMbW7b2dgWr2O4nTa4AzOFiMcY8vUOeomedeCTffVQj9H3z5--nZ0Xq6_Li7PTVWFkJVlhSwqiq2zeqGMWJBOUEUsULxtVto0STcV3CCklaaiwULWypKxSuYoaDD9GH_e-49z0tjV2mCJ4PUbXQ9zqAE7_-TK4jV6Hn5rXghIlssG7B4MYfsw2Tbp3yVjvYbBhTpoKLgjLaP0fKJUl4UTJjL79C70Oc8yff08xIVS2zNT7PWViSCna7jA3JXoXt97Fre_jzvCb3zc9oI_5ZoDugVvn7fYfVnq5ujh9NC32Gpcme3fQQLzRpeJK6qsvS315fsWkqKgm_BcqAsVe</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1412447210</pqid></control><display><type>article</type><title>Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>McGivern, Jered V. ; Patitucci, Teresa N. ; Nord, Joshua A. ; Barabas, Marie-Elizabeth A. ; Stucky, Cheryl L. ; Ebert, Allison D.</creator><creatorcontrib>McGivern, Jered V. ; Patitucci, Teresa N. ; Nord, Joshua A. ; Barabas, Marie-Elizabeth A. ; Stucky, Cheryl L. ; Ebert, Allison D.</creatorcontrib><description>Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMAΔ7 mouse spinal cord and from SMA‐induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis‐regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology.</description><identifier>ISSN: 0894-1491</identifier><identifier>EISSN: 1098-1136</identifier><identifier>DOI: 10.1002/glia.22522</identifier><identifier>PMID: 23839956</identifier><identifier>CODEN: GLIAEJ</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adenosine Triphosphate - pharmacology ; Age Factors ; Aldehyde Dehydrogenase - metabolism ; Amyotrophic lateral sclerosis ; Analysis of Variance ; Animals ; Animals, Newborn ; astrocyte activation ; Astrocytes - drug effects ; Astrocytes - metabolism ; ATP ; Calcium ; Calcium - metabolism ; cell autonomous ; Cell Line, Transformed ; Choline O-Acetyltransferase - metabolism ; Disease Models, Animal ; Gene Expression Regulation, Developmental - genetics ; Glial Cell Line-Derived Neurotrophic Factor - metabolism ; Glial Fibrillary Acidic Protein - metabolism ; Humans ; Mice ; Mice, Transgenic ; motor neurons ; Muscular Atrophy, Spinal - genetics ; Muscular Atrophy, Spinal - pathology ; Mutation - genetics ; Nestin - metabolism ; Neurons ; Pathology ; Pluripotent Stem Cells - metabolism ; Receptors, Purinergic P2Y2 - metabolism ; Rodents ; S100 Proteins - metabolism ; Spinal cord ; Spinal Cord - cytology ; stem cells ; Survival of Motor Neuron 1 Protein - genetics ; Survival of Motor Neuron 2 Protein - metabolism</subject><ispartof>Glia, 2013-09, Vol.61 (9), p.1418-1428</ispartof><rights>Copyright © 2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5852-e61a4f8e225f2ea524120e0736b76db74b8361a40650b14ea8d5612878d549ac3</citedby><cites>FETCH-LOGICAL-c5852-e61a4f8e225f2ea524120e0736b76db74b8361a40650b14ea8d5612878d549ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fglia.22522$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fglia.22522$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23839956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McGivern, Jered V.</creatorcontrib><creatorcontrib>Patitucci, Teresa N.</creatorcontrib><creatorcontrib>Nord, Joshua A.</creatorcontrib><creatorcontrib>Barabas, Marie-Elizabeth A.</creatorcontrib><creatorcontrib>Stucky, Cheryl L.</creatorcontrib><creatorcontrib>Ebert, Allison D.</creatorcontrib><title>Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production</title><title>Glia</title><addtitle>Glia</addtitle><description>Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMAΔ7 mouse spinal cord and from SMA‐induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis‐regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology.</description><subject>Adenosine Triphosphate - pharmacology</subject><subject>Age Factors</subject><subject>Aldehyde Dehydrogenase - metabolism</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>astrocyte activation</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>ATP</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>cell autonomous</subject><subject>Cell Line, Transformed</subject><subject>Choline O-Acetyltransferase - metabolism</subject><subject>Disease Models, Animal</subject><subject>Gene Expression Regulation, Developmental - genetics</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - metabolism</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>motor neurons</subject><subject>Muscular Atrophy, Spinal - genetics</subject><subject>Muscular Atrophy, Spinal - pathology</subject><subject>Mutation - genetics</subject><subject>Nestin - metabolism</subject><subject>Neurons</subject><subject>Pathology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Receptors, Purinergic P2Y2 - metabolism</subject><subject>Rodents</subject><subject>S100 Proteins - metabolism</subject><subject>Spinal cord</subject><subject>Spinal Cord - cytology</subject><subject>stem cells</subject><subject>Survival of Motor Neuron 1 Protein - genetics</subject><subject>Survival of Motor Neuron 2 Protein - metabolism</subject><issn>0894-1491</issn><issn>1098-1136</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EokvhwgdAlrggpBT_jZMLUlXBttIKDgX1aE0cZ9etEwc7od1vj7fbroAD4jQe-_eeZvwQek3JCSWEfVh7ByeMScaeoAUldVVQysunaEGqWhRU1PQIvUjpmhCaG_UcHTFe8bqW5QLdXI5uAI_7OZnZQ8QwxTButhhSPpjtZBO2dxvXuAlDM4TYZ9iAN27ucbTrrJlcGDAMbW7b2dgWr2O4nTa4AzOFiMcY8vUOeomedeCTffVQj9H3z5--nZ0Xq6_Li7PTVWFkJVlhSwqiq2zeqGMWJBOUEUsULxtVto0STcV3CCklaaiwULWypKxSuYoaDD9GH_e-49z0tjV2mCJ4PUbXQ9zqAE7_-TK4jV6Hn5rXghIlssG7B4MYfsw2Tbp3yVjvYbBhTpoKLgjLaP0fKJUl4UTJjL79C70Oc8yff08xIVS2zNT7PWViSCna7jA3JXoXt97Fre_jzvCb3zc9oI_5ZoDugVvn7fYfVnq5ujh9NC32Gpcme3fQQLzRpeJK6qsvS315fsWkqKgm_BcqAsVe</recordid><startdate>201309</startdate><enddate>201309</enddate><creator>McGivern, Jered V.</creator><creator>Patitucci, Teresa N.</creator><creator>Nord, Joshua A.</creator><creator>Barabas, Marie-Elizabeth A.</creator><creator>Stucky, Cheryl L.</creator><creator>Ebert, Allison D.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>7QP</scope><scope>5PM</scope></search><sort><creationdate>201309</creationdate><title>Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production</title><author>McGivern, Jered V. ; Patitucci, Teresa N. ; Nord, Joshua A. ; Barabas, Marie-Elizabeth A. ; Stucky, Cheryl L. ; Ebert, Allison D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5852-e61a4f8e225f2ea524120e0736b76db74b8361a40650b14ea8d5612878d549ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenosine Triphosphate - pharmacology</topic><topic>Age Factors</topic><topic>Aldehyde Dehydrogenase - metabolism</topic><topic>Amyotrophic lateral sclerosis</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>astrocyte activation</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>ATP</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>cell autonomous</topic><topic>Cell Line, Transformed</topic><topic>Choline O-Acetyltransferase - metabolism</topic><topic>Disease Models, Animal</topic><topic>Gene Expression Regulation, Developmental - genetics</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - metabolism</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>motor neurons</topic><topic>Muscular Atrophy, Spinal - genetics</topic><topic>Muscular Atrophy, Spinal - pathology</topic><topic>Mutation - genetics</topic><topic>Nestin - metabolism</topic><topic>Neurons</topic><topic>Pathology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Receptors, Purinergic P2Y2 - metabolism</topic><topic>Rodents</topic><topic>S100 Proteins - metabolism</topic><topic>Spinal cord</topic><topic>Spinal Cord - cytology</topic><topic>stem cells</topic><topic>Survival of Motor Neuron 1 Protein - genetics</topic><topic>Survival of Motor Neuron 2 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McGivern, Jered V.</creatorcontrib><creatorcontrib>Patitucci, Teresa N.</creatorcontrib><creatorcontrib>Nord, Joshua A.</creatorcontrib><creatorcontrib>Barabas, Marie-Elizabeth A.</creatorcontrib><creatorcontrib>Stucky, Cheryl L.</creatorcontrib><creatorcontrib>Ebert, Allison D.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Glia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McGivern, Jered V.</au><au>Patitucci, Teresa N.</au><au>Nord, Joshua A.</au><au>Barabas, Marie-Elizabeth A.</au><au>Stucky, Cheryl L.</au><au>Ebert, Allison D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production</atitle><jtitle>Glia</jtitle><addtitle>Glia</addtitle><date>2013-09</date><risdate>2013</risdate><volume>61</volume><issue>9</issue><spage>1418</spage><epage>1428</epage><pages>1418-1428</pages><issn>0894-1491</issn><eissn>1098-1136</eissn><coden>GLIAEJ</coden><abstract>Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMAΔ7 mouse spinal cord and from SMA‐induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis‐regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23839956</pmid><doi>10.1002/glia.22522</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0894-1491 |
| ispartof | Glia, 2013-09, Vol.61 (9), p.1418-1428 |
| issn | 0894-1491 1098-1136 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3941074 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adenosine Triphosphate - pharmacology Age Factors Aldehyde Dehydrogenase - metabolism Amyotrophic lateral sclerosis Analysis of Variance Animals Animals, Newborn astrocyte activation Astrocytes - drug effects Astrocytes - metabolism ATP Calcium Calcium - metabolism cell autonomous Cell Line, Transformed Choline O-Acetyltransferase - metabolism Disease Models, Animal Gene Expression Regulation, Developmental - genetics Glial Cell Line-Derived Neurotrophic Factor - metabolism Glial Fibrillary Acidic Protein - metabolism Humans Mice Mice, Transgenic motor neurons Muscular Atrophy, Spinal - genetics Muscular Atrophy, Spinal - pathology Mutation - genetics Nestin - metabolism Neurons Pathology Pluripotent Stem Cells - metabolism Receptors, Purinergic P2Y2 - metabolism Rodents S100 Proteins - metabolism Spinal cord Spinal Cord - cytology stem cells Survival of Motor Neuron 1 Protein - genetics Survival of Motor Neuron 2 Protein - metabolism |
| title | Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T00%3A56%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Spinal%20muscular%20atrophy%20astrocytes%20exhibit%20abnormal%20calcium%20regulation%20and%20reduced%20growth%20factor%20production&rft.jtitle=Glia&rft.au=McGivern,%20Jered%20V.&rft.date=2013-09&rft.volume=61&rft.issue=9&rft.spage=1418&rft.epage=1428&rft.pages=1418-1428&rft.issn=0894-1491&rft.eissn=1098-1136&rft.coden=GLIAEJ&rft_id=info:doi/10.1002/glia.22522&rft_dat=%3Cproquest_pubme%3E3028560771%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1412447210&rft_id=info:pmid/23839956&rfr_iscdi=true |