Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease
Identifieur interne : 000870 ( Main/Exploration ); précédent : 000869; suivant : 000871Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease
Auteurs : Catherine Kielar ; Thomas M. Wishart ; Alice Palmer ; Sybille Dihanich ; Andrew M. Wong ; Shannon L. Macauley ; Chun-Hung Chan ; Mark S. Sands ; David A. Pearce ; Jonathan D. Cooper ; Thomas H. Gillingwater [Royaume-Uni]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2009-11-01.
Abstract
Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1/ model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs.
Url:
DOI: 10.1093/hmg/ddp355
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease</title><author><name sortKey="Kielar, Catherine" sort="Kielar, Catherine" uniqKey="Kielar C" first="Catherine" last="Kielar">Catherine Kielar</name></author><author><name sortKey="Wishart, Thomas M" sort="Wishart, Thomas M" uniqKey="Wishart T" first="Thomas M." last="Wishart">Thomas M. Wishart</name></author><author><name sortKey="Palmer, Alice" sort="Palmer, Alice" uniqKey="Palmer A" first="Alice" last="Palmer">Alice Palmer</name></author><author><name sortKey="Dihanich, Sybille" sort="Dihanich, Sybille" uniqKey="Dihanich S" first="Sybille" last="Dihanich">Sybille Dihanich</name></author><author><name sortKey="Wong, Andrew M" sort="Wong, Andrew M" uniqKey="Wong A" first="Andrew M." last="Wong">Andrew M. Wong</name></author><author><name sortKey="Macauley, Shannon L" sort="Macauley, Shannon L" uniqKey="Macauley S" first="Shannon L." last="Macauley">Shannon L. Macauley</name></author><author><name sortKey="Chan, Chun Hung" sort="Chan, Chun Hung" uniqKey="Chan C" first="Chun-Hung" last="Chan">Chun-Hung Chan</name></author><author><name sortKey="Sands, Mark S" sort="Sands, Mark S" uniqKey="Sands M" first="Mark S." last="Sands">Mark S. Sands</name></author><author><name sortKey="Pearce, David A" sort="Pearce, David A" uniqKey="Pearce D" first="David A." last="Pearce">David A. Pearce</name></author><author><name sortKey="Cooper, Jonathan D" sort="Cooper, Jonathan D" uniqKey="Cooper J" first="Jonathan D." last="Cooper">Jonathan D. Cooper</name></author><author><name sortKey="Gillingwater, Thomas H" sort="Gillingwater, Thomas H" uniqKey="Gillingwater T" first="Thomas H." last="Gillingwater">Thomas H. Gillingwater</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:66192E28B1A3966517E8D1E3289579D89F041C8E</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1093/hmg/ddp355</idno><idno type="url">https://api.istex.fr/document/66192E28B1A3966517E8D1E3289579D89F041C8E/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002772</idno><idno type="wicri:Area/Main/Curation">002428</idno><idno type="wicri:Area/Main/Exploration">000870</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease</title><author><name sortKey="Kielar, Catherine" sort="Kielar, Catherine" uniqKey="Kielar C" first="Catherine" last="Kielar">Catherine Kielar</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Wishart, Thomas M" sort="Wishart, Thomas M" uniqKey="Wishart T" first="Thomas M." last="Wishart">Thomas M. Wishart</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Palmer, Alice" sort="Palmer, Alice" uniqKey="Palmer A" first="Alice" last="Palmer">Alice Palmer</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Dihanich, Sybille" sort="Dihanich, Sybille" uniqKey="Dihanich S" first="Sybille" last="Dihanich">Sybille Dihanich</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Wong, Andrew M" sort="Wong, Andrew M" uniqKey="Wong A" first="Andrew M." last="Wong">Andrew M. Wong</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Macauley, Shannon L" sort="Macauley, Shannon L" uniqKey="Macauley S" first="Shannon L." last="Macauley">Shannon L. Macauley</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Chan, Chun Hung" sort="Chan, Chun Hung" uniqKey="Chan C" first="Chun-Hung" last="Chan">Chun-Hung Chan</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Sands, Mark S" sort="Sands, Mark S" uniqKey="Sands M" first="Mark S." last="Sands">Mark S. Sands</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Pearce, David A" sort="Pearce, David A" uniqKey="Pearce D" first="David A." last="Pearce">David A. Pearce</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Cooper, Jonathan D" sort="Cooper, Jonathan D" uniqKey="Cooper J" first="Jonathan D." last="Cooper">Jonathan D. Cooper</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Gillingwater, Thomas H" sort="Gillingwater, Thomas H" uniqKey="Gillingwater T" first="Thomas H." last="Gillingwater">Thomas H. Gillingwater</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-11-01">2009-11-01</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">21</biblScope><biblScope unit="page" from="4066">4066</biblScope><biblScope unit="page" to="4080">4080</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">66192E28B1A3966517E8D1E3289579D89F041C8E</idno><idno type="DOI">10.1093/hmg/ddp355</idno><idno type="ArticleID">ddp355</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1/ model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><noCountry><name sortKey="Chan, Chun Hung" sort="Chan, Chun Hung" uniqKey="Chan C" first="Chun-Hung" last="Chan">Chun-Hung Chan</name><name sortKey="Cooper, Jonathan D" sort="Cooper, Jonathan D" uniqKey="Cooper J" first="Jonathan D." last="Cooper">Jonathan D. Cooper</name><name sortKey="Dihanich, Sybille" sort="Dihanich, Sybille" uniqKey="Dihanich S" first="Sybille" last="Dihanich">Sybille Dihanich</name><name sortKey="Kielar, Catherine" sort="Kielar, Catherine" uniqKey="Kielar C" first="Catherine" last="Kielar">Catherine Kielar</name><name sortKey="Macauley, Shannon L" sort="Macauley, Shannon L" uniqKey="Macauley S" first="Shannon L." last="Macauley">Shannon L. Macauley</name><name sortKey="Palmer, Alice" sort="Palmer, Alice" uniqKey="Palmer A" first="Alice" last="Palmer">Alice Palmer</name><name sortKey="Pearce, David A" sort="Pearce, David A" uniqKey="Pearce D" first="David A." last="Pearce">David A. Pearce</name><name sortKey="Sands, Mark S" sort="Sands, Mark S" uniqKey="Sands M" first="Mark S." last="Sands">Mark S. Sands</name><name sortKey="Wishart, Thomas M" sort="Wishart, Thomas M" uniqKey="Wishart T" first="Thomas M." last="Wishart">Thomas M. Wishart</name><name sortKey="Wong, Andrew M" sort="Wong, Andrew M" uniqKey="Wong A" first="Andrew M." last="Wong">Andrew M. Wong</name></noCountry><country name="Royaume-Uni"><noRegion><name sortKey="Gillingwater, Thomas H" sort="Gillingwater, Thomas H" uniqKey="Gillingwater T" first="Thomas H." last="Gillingwater">Thomas H. Gillingwater</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000870 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000870 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:66192E28B1A3966517E8D1E3289579D89F041C8E
|texte= Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease
}}
| This area was generated with Dilib version V0.6.23. |  |