Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease.
Identifieur interne : 000065 ( Hal/Curation ); précédent : 000064; suivant : 000066Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease.
Auteurs : Alireza Kashani [France] ; Catalina Betancur [France] ; Bruno Giros [France] ; Etienne Hirsch [France] ; Salah El Mestikawy [France]Source :
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Abstract
Glutamatergic pathways play a key role in the functional organization of neuronal circuits involved in Parkinson disease (PD). Recently, three vesicular glutamate transporters (VGLUT1-3) were identified. VGLUT1 and VGLUT2 are responsible for the uploading of glutamate into synaptic vesicles and are the first specific markers of glutamatergic neurons available. Here, we analyzed the expression of VGLUT1 and VGLUT2 in autopsy tissues of PD patients and matched controls using Western blot and immunoautoradiography. VGLUT1 and VGLUT2 expression was increased in the Parkinsonian putamen by 24% and 29%, respectively (p<0.01). In contrast, only VGLUT1 was dramatically decreased in the prefrontal and temporal cortex of PD patients (approximately 50%, p<0.01 and p<0.001, respectively). These findings demonstrate the existence of profound alterations of glutamatergic transmission in PD, which are likely to contribute to the motor and cognitive impairments associated with the disease, and should thus be taken into account in the treatment of PD.
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DOI: 10.1016/j.neurobiolaging.2006.02.010
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<front><div type="abstract" xml:lang="en">Glutamatergic pathways play a key role in the functional organization of neuronal circuits involved in Parkinson disease (PD). Recently, three vesicular glutamate transporters (VGLUT1-3) were identified. VGLUT1 and VGLUT2 are responsible for the uploading of glutamate into synaptic vesicles and are the first specific markers of glutamatergic neurons available. Here, we analyzed the expression of VGLUT1 and VGLUT2 in autopsy tissues of PD patients and matched controls using Western blot and immunoautoradiography. VGLUT1 and VGLUT2 expression was increased in the Parkinsonian putamen by 24% and 29%, respectively (p<0.01). In contrast, only VGLUT1 was dramatically decreased in the prefrontal and temporal cortex of PD patients (approximately 50%, p<0.01 and p<0.001, respectively). These findings demonstrate the existence of profound alterations of glutamatergic transmission in PD, which are likely to contribute to the motor and cognitive impairments associated with the disease, and should thus be taken into account in the treatment of PD.</div>
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<funder>This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM) and by grants from Association France Parkinson and Fédération pour la Recherche sur le Cerveau. AK was supported by a fellowship from Association France Alzheimer.</funder>
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<name key="111046"><persName><forename>Catalina</forename>
<surname>Betancur</surname>
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<idno type="halRefHtml">Neurobiol Aging, 2007, 28 (4), pp.568-78. <10.1016/j.neurobiolaging.2006.02.010></idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease.</title>
<author role="aut"><persName><forename type="first">Alireza</forename>
<surname>Kashani</surname>
</persName>
<idno type="halauthorid">188150</idno>
<affiliation ref="#struct-2881"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Catalina</forename>
<surname>Betancur</surname>
</persName>
<idno type="halauthorid">117624</idno>
<affiliation ref="#struct-2881"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Bruno</forename>
<surname>Giros</surname>
</persName>
<idno type="halauthorid">157784</idno>
<affiliation ref="#struct-2881"></affiliation>
</author>
<author role="aut"><persName><forename type="first">Etienne</forename>
<forename type="middle">C.</forename>
<surname>Hirsch</surname>
</persName>
<idno type="halauthorid">188151</idno>
<affiliation ref="#struct-3037"></affiliation>
</author>
<author role="crp"><persName><forename type="first">Salah</forename>
<surname>El Mestikawy</surname>
</persName>
<email type="md5">72dd00bcfe664fa10c4deef430519f9f</email>
<email type="domain">creteil.inserm.fr</email>
<idno type="halauthorid">188152</idno>
<affiliation ref="#struct-2881"></affiliation>
</author>
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<monogr><idno type="halJournalId" status="INCOMING">27025</idno>
<title level="j">Neurobiol Aging</title>
<imprint><biblScope unit="volume">28</biblScope>
<biblScope unit="issue">4</biblScope>
<biblScope unit="pp">568-78</biblScope>
<date type="datePub">2007-04</date>
<date type="dateEpub">2006-03-24</date>
</imprint>
</monogr>
<idno type="doi">10.1016/j.neurobiolaging.2006.02.010</idno>
<idno type="pubmed">16563567</idno>
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<profileDesc><langUsage><language ident="en">English</language>
</langUsage>
<textClass><keywords scheme="author"><term xml:lang="en">Human</term>
<term xml:lang="en">Parkinson disease</term>
<term xml:lang="en">Vesicular glutamate transporter</term>
<term xml:lang="en">VGLUT1</term>
<term xml:lang="en">VGLUT2</term>
<term xml:lang="en">Prefrontal cortex</term>
<term xml:lang="en">Temporal cortex</term>
<term xml:lang="en">Putamen</term>
<term xml:lang="en">Western blot</term>
<term xml:lang="en">Immunoautoradiography</term>
</keywords>
<classCode scheme="mesh">Aged</classCode>
<classCode scheme="mesh">Aged, 80 and over</classCode>
<classCode scheme="mesh">Case-Control Studies</classCode>
<classCode scheme="mesh">Female</classCode>
<classCode scheme="mesh">Gene Expression Regulation</classCode>
<classCode scheme="mesh">Humans</classCode>
<classCode scheme="mesh">Male</classCode>
<classCode scheme="mesh">Middle Aged</classCode>
<classCode scheme="mesh">Nerve Tissue Proteins</classCode>
<classCode scheme="mesh">Parkinson Disease</classCode>
<classCode scheme="mesh">Postmortem Changes</classCode>
<classCode scheme="mesh">Vesicular Glutamate Transport Protein 1</classCode>
<classCode scheme="mesh">Autoradiography</classCode>
<classCode scheme="mesh">Blotting, Western</classCode>
<classCode scheme="mesh">Brain</classCode>
<classCode scheme="halDomain" n="sdv.neu">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">Glutamatergic pathways play a key role in the functional organization of neuronal circuits involved in Parkinson disease (PD). Recently, three vesicular glutamate transporters (VGLUT1-3) were identified. VGLUT1 and VGLUT2 are responsible for the uploading of glutamate into synaptic vesicles and are the first specific markers of glutamatergic neurons available. Here, we analyzed the expression of VGLUT1 and VGLUT2 in autopsy tissues of PD patients and matched controls using Western blot and immunoautoradiography. VGLUT1 and VGLUT2 expression was increased in the Parkinsonian putamen by 24% and 29%, respectively (p<0.01). In contrast, only VGLUT1 was dramatically decreased in the prefrontal and temporal cortex of PD patients (approximately 50%, p<0.01 and p<0.001, respectively). These findings demonstrate the existence of profound alterations of glutamatergic transmission in PD, which are likely to contribute to the motor and cognitive impairments associated with the disease, and should thus be taken into account in the treatment of PD.</abstract>
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