The effect of striatal pre-enkephalin overexpression in the basal ganglia of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
Identifieur interne : 000B83 ( Main/Exploration ); précédent : 000B82; suivant : 000B84The effect of striatal pre-enkephalin overexpression in the basal ganglia of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
Auteurs : Stéphanie Bissonnette [Canada] ; Sophie Muratot [Canada] ; Nathalie Vernoux [Canada] ; François Bezeau [Canada] ; Frédéric Calon [Canada] ; Sébastien S. Hebert [Canada] ; Pershia Samadi [Canada]Source :
- European journal of neuroscience : (Print) [ 0953-816X ] ; 2014.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The midbrain dopamine (DA) cell death underlying Parkinson's disease (PD) is associated with upregulation of pre-enkephalin (pENK) in striatopallidal neurons. Our previous results obtained with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys suggest that increased striatal expression of pENK mRNA is a compensatory mechanism to alleviate PD-related motor symptoms. In this study, we tested the hypothesis that increased pENK expression in the striatum protects against the neurotoxic insults of MPTP in mice. To this end, recombinant adeno-associated virus serotype 2 also containing green fluorescent protein was used to overexpress pENK prior to DA depletion. Our results showed that overexpression of pENK in the striatum of MPTP mice induced: (i) increased levels of the opioid peptide enkephalin (ENK) in the striatum; (ii) higher densities of ENK-positive fibers in both the globus pallidus (GP) and the substantia nigra; (iii) higher locomotor activity; and (iv) a higher density of striatal tyrosine hydroxylase-positive fibers in the striatum. In addition, striatal overexpression of pENK in MPTP -treated mice led to 52 and 43% higher DA concentrations and DA turnover, respectively, in the GP compared to sham-treated MPTP mice. These observations are in agreement with the idea that increased expression of pENK at an early stage of disease can improve PD symptoms.
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Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation></author><author><name sortKey="Muratot, Sophie" sort="Muratot, Sophie" uniqKey="Muratot S" first="Sophie" last="Muratot">Sophie Muratot</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation></author><author><name sortKey="Vernoux, Nathalie" sort="Vernoux, Nathalie" uniqKey="Vernoux N" first="Nathalie" last="Vernoux">Nathalie Vernoux</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation></author><author><name sortKey="Bezeau, Francois" sort="Bezeau, Francois" uniqKey="Bezeau F" first="François" last="Bezeau">François Bezeau</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Département de psychiatrie et de neurosciences, Faculté de Médicine, Université Laval</s1><s2>Quebec, QC</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, QC</wicri:noRegion></affiliation></author><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculté de pharmacie, Université Laval</s1><s2>Québec, QC</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC</wicri:noRegion></affiliation></author><author><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hebert">Sébastien S. Hebert</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Département de psychiatrie et de neurosciences, Faculté de Médicine, Université Laval</s1><s2>Quebec, QC</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, QC</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Axe Neurosciences, Centre de recherche du CHU de Quebec, CHUL, 2705, boul. Laurier</s1><s2>Québec, QC, G1V 4G2</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, QC, G1V 4G2</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Département de psychiatrie et de neurosciences, Faculté de Médicine, Université Laval</s1><s2>Quebec, QC</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, QC</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">European journal of neuroscience : (Print)</title><title level="j" type="abbreviated">Eur. j. neurosci. : (Print)</title><idno type="ISSN">0953-816X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">European journal of neuroscience : (Print)</title><title level="j" type="abbreviated">Eur. j. neurosci. : (Print)</title><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Animal model</term><term>Basal ganglion</term><term>Corpus striatum</term><term>Degeneration</term><term>Dopamine</term><term>Enkephalin</term><term>Gene overexpression</term><term>Mouse</term><term>Opioid peptide</term><term>Pallidum</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Corps strié</term><term>Enképhaline</term><term>Surexpression génique</term><term>Noyau gris central</term><term>Modèle animal</term><term>Dopamine</term><term>Pallidum</term><term>Dégénérescence</term><term>Maladie de Parkinson</term><term>Peptide opioïde</term><term>Souris</term><term>Animal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The midbrain dopamine (DA) cell death underlying Parkinson's disease (PD) is associated with upregulation of pre-enkephalin (pENK) in striatopallidal neurons. Our previous results obtained with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys suggest that increased striatal expression of pENK mRNA is a compensatory mechanism to alleviate PD-related motor symptoms. In this study, we tested the hypothesis that increased pENK expression in the striatum protects against the neurotoxic insults of MPTP in mice. To this end, recombinant adeno-associated virus serotype 2 also containing green fluorescent protein was used to overexpress pENK prior to DA depletion. Our results showed that overexpression of pENK in the striatum of MPTP mice induced: (i) increased levels of the opioid peptide enkephalin (ENK) in the striatum; (ii) higher densities of ENK-positive fibers in both the globus pallidus (GP) and the substantia nigra; (iii) higher locomotor activity; and (iv) a higher density of striatal tyrosine hydroxylase-positive fibers in the striatum. In addition, striatal overexpression of pENK in MPTP -treated mice led to 52 and 43% higher DA concentrations and DA turnover, respectively, in the GP compared to sham-treated MPTP mice. These observations are in agreement with the idea that increased expression of pENK at an early stage of disease can improve PD symptoms.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Bissonnette, Stephanie" sort="Bissonnette, Stephanie" uniqKey="Bissonnette S" first="Stéphanie" last="Bissonnette">Stéphanie Bissonnette</name></noRegion><name sortKey="Bezeau, Francois" sort="Bezeau, Francois" uniqKey="Bezeau F" first="François" last="Bezeau">François Bezeau</name><name sortKey="Bezeau, Francois" sort="Bezeau, Francois" uniqKey="Bezeau F" first="François" last="Bezeau">François Bezeau</name><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hebert">Sébastien S. Hebert</name><name sortKey="Hebert, Sebastien S" sort="Hebert, Sebastien S" uniqKey="Hebert S" first="Sébastien S." last="Hebert">Sébastien S. Hebert</name><name sortKey="Muratot, Sophie" sort="Muratot, Sophie" uniqKey="Muratot S" first="Sophie" last="Muratot">Sophie Muratot</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><name sortKey="Vernoux, Nathalie" sort="Vernoux, Nathalie" uniqKey="Vernoux N" first="Nathalie" last="Vernoux">Nathalie Vernoux</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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