Transient Muscarinic and Glutamatergic Stimulation of Neural Stem Cells Trigger Acute and Persistent Changes in Differentiation
Identifieur interne : 001878 ( Pmc/Curation ); précédent : 001877; suivant : 001879Transient Muscarinic and Glutamatergic Stimulation of Neural Stem Cells Trigger Acute and Persistent Changes in Differentiation
Auteurs : Ranmal A. Samarasinghe ; Prasad S. Kanuparthi ; J. Timothy Greenamyre ; Donald B. Defranco ; Roberto Di MaioSource :
- Neurobiology of disease [ 0969-9961 ] ; 2014.
Abstract
While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca++ transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs.
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DOI: 10.1016/j.nbd.2014.06.020
PubMed: 25003306
PubMed Central: 4152385
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Ranmal A. Samarasinghe<affiliation><nlm:aff id="A2">University of California Los Angeles, Department of Neurology</nlm:aff><wicri:noCountry code="subfield">Department of Neurology</wicri:noCountry></affiliation>Le document en format XML
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Kanuparthi</name><affiliation><nlm:aff id="A1">University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</nlm:aff></affiliation></author><author><name sortKey="Greenamyre, J Timothy" sort="Greenamyre, J Timothy" uniqKey="Greenamyre J" first="J. Timothy" last="Greenamyre">J. Timothy Greenamyre</name><affiliation><nlm:aff id="A3">University of Pittsburgh School of Medicine-Pittsburgh Institute of Neurodegenerative Diseases</nlm:aff></affiliation></author><author><name sortKey="Defranco, Donald B" sort="Defranco, Donald B" uniqKey="Defranco D" first="Donald B." last="Defranco">Donald B. Defranco</name><affiliation><nlm:aff id="A1">University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</nlm:aff></affiliation></author><author><name sortKey="Di Maio, Roberto" sort="Di Maio, Roberto" uniqKey="Di Maio R" first="Roberto" last="Di Maio">Roberto Di Maio</name><affiliation><nlm:aff id="A3">University of Pittsburgh School of Medicine-Pittsburgh Institute of Neurodegenerative Diseases</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25003306</idno><idno type="pmc">4152385</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152385</idno><idno type="RBID">PMC:4152385</idno><idno type="doi">10.1016/j.nbd.2014.06.020</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001903</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001903</idno><idno type="wicri:Area/Pmc/Curation">001878</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001878</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transient Muscarinic and Glutamatergic Stimulation of Neural Stem Cells Trigger Acute and Persistent Changes in Differentiation</title><author><name sortKey="Samarasinghe, Ranmal A" sort="Samarasinghe, Ranmal A" uniqKey="Samarasinghe R" first="Ranmal A." last="Samarasinghe">Ranmal A. Samarasinghe</name><affiliation><nlm:aff id="A1">University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</nlm:aff></affiliation><affiliation><nlm:aff id="A2">University of California Los Angeles, Department of Neurology</nlm:aff><wicri:noCountry code="subfield">Department of Neurology</wicri:noCountry></affiliation></author><author><name sortKey="Kanuparthi, Prasad S" sort="Kanuparthi, Prasad S" uniqKey="Kanuparthi P" first="Prasad S." last="Kanuparthi">Prasad S. Kanuparthi</name><affiliation><nlm:aff id="A1">University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</nlm:aff></affiliation></author><author><name sortKey="Greenamyre, J Timothy" sort="Greenamyre, J Timothy" uniqKey="Greenamyre J" first="J. Timothy" last="Greenamyre">J. Timothy Greenamyre</name><affiliation><nlm:aff id="A3">University of Pittsburgh School of Medicine-Pittsburgh Institute of Neurodegenerative Diseases</nlm:aff></affiliation></author><author><name sortKey="Defranco, Donald B" sort="Defranco, Donald B" uniqKey="Defranco D" first="Donald B." last="Defranco">Donald B. Defranco</name><affiliation><nlm:aff id="A1">University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</nlm:aff></affiliation></author><author><name sortKey="Di Maio, Roberto" sort="Di Maio, Roberto" uniqKey="Di Maio R" first="Roberto" last="Di Maio">Roberto Di Maio</name><affiliation><nlm:aff id="A3">University of Pittsburgh School of Medicine-Pittsburgh Institute of Neurodegenerative Diseases</nlm:aff></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="ISSN">0969-9961</idno><idno type="eISSN">1095-953X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca<sup>++</sup> transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9500169</journal-id><journal-id journal-id-type="pubmed-jr-id">20475</journal-id><journal-id journal-id-type="nlm-ta">Neurobiol Dis</journal-id><journal-id journal-id-type="iso-abbrev">Neurobiol. Dis.</journal-id><journal-title-group><journal-title>Neurobiology of disease</journal-title></journal-title-group><issn pub-type="ppub">0969-9961</issn><issn pub-type="epub">1095-953X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25003306</article-id><article-id pub-id-type="pmc">4152385</article-id><article-id pub-id-type="doi">10.1016/j.nbd.2014.06.020</article-id><article-id pub-id-type="manuscript">NIHMS612531</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Transient Muscarinic and Glutamatergic Stimulation of Neural Stem Cells Trigger Acute and Persistent Changes in Differentiation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Samarasinghe</surname><given-names>Ranmal A.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kanuparthi</surname><given-names>Prasad S.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Greenamyre</surname><given-names>J. Timothy</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>DeFranco</surname><given-names>Donald B.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Di Maio</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>University of Pittsburgh School of Medicine Department of Pharmacology and Chemical Biology</aff><aff id="A2"><label>2</label>University of California Los Angeles, Department of Neurology</aff><aff id="A3"><label>3</label>University of Pittsburgh School of Medicine-Pittsburgh Institute of Neurodegenerative Diseases</aff><author-notes><corresp id="FN1">Contact: Ranmal A. Samarasinghe. <email>ranmals@gmail.com</email></corresp><fn id="FN2" fn-type="equal"><label>*</label><p>Co-corresponding and co-senior authors</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>7</day><month>8</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>06</day><month>7</month><year>2014</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>10</month><year>2015</year></pub-date><volume>70</volume><fpage>252</fpage><lpage>261</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.nbd.2014.06.020</pmc-comment>
<permissions><copyright-statement>© 2014 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p id="P1">While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca<sup>++</sup> transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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