Compacted DNA nanoparticle gene transfer of GDNF to the rat striatum enhances the survival of grafted fetal dopamine neurons.
Identifieur interne : 002810 ( Main/Exploration ); précédent : 002809; suivant : 002811Compacted DNA nanoparticle gene transfer of GDNF to the rat striatum enhances the survival of grafted fetal dopamine neurons.
Auteurs : David M. Yurek [États-Unis] ; Anita M. Flectcher ; Tomasz H. Kowalczyk ; Linas Padegimas ; Mark J. CooperSource :
- Cell transplantation [ 1555-3892 ] ; 2009.
Descripteurs français
- KwdFr :
- ADN (administration et posologie), Activité motrice (), Animaux, Comportement animal, Corps strié (anatomopathologie), Corps strié (métabolisme), Dopamine (métabolisme), Facteur neurotrophique dérivé des cellules gliales (génétique), Facteur neurotrophique dérivé des cellules gliales (métabolisme), Maladie de Parkinson (), Modèles animaux de maladie humaine, Mâle, Mésencéphale (transplantation), Nanoparticules (), Neurones (cytologie), Neurones (métabolisme), Neurones (transplantation), Plasmides (métabolisme), Polylysine (), Polyéthylène glycols (), Rat Sprague-Dawley, Rats, Techniques de transfert de gènes, Test du rotarod, Transplantation de tissu cérébral, Transplantation de tissu foetal.
- MESH :
- administration et posologie : ADN.
- anatomopathologie : Corps strié.
- cytologie : Neurones.
- génétique : Facteur neurotrophique dérivé des cellules gliales.
- métabolisme : Corps strié, Dopamine, Facteur neurotrophique dérivé des cellules gliales, Neurones, Plasmides.
- Activité motrice, Animaux, Comportement animal, Maladie de Parkinson, Modèles animaux de maladie humaine, Mâle, Mésencéphale, Nanoparticules, Neurones, Polylysine, Polyéthylène glycols, Rat Sprague-Dawley, Rats, Techniques de transfert de gènes, Test du rotarod, Transplantation de tissu cérébral, Transplantation de tissu foetal.
English descriptors
- KwdEn :
- Animals, Behavior, Animal, Brain Tissue Transplantation, Corpus Striatum (metabolism), Corpus Striatum (pathology), DNA (administration & dosage), Disease Models, Animal, Dopamine (metabolism), Fetal Tissue Transplantation, Gene Transfer Techniques, Glial Cell Line-Derived Neurotrophic Factor (genetics), Glial Cell Line-Derived Neurotrophic Factor (metabolism), Male, Mesencephalon (transplantation), Motor Activity (drug effects), Nanoparticles (chemistry), Neurons (cytology), Neurons (metabolism), Neurons (transplantation), Parkinson Disease (therapy), Plasmids (metabolism), Polyethylene Glycols (chemistry), Polylysine (chemistry), Rats, Rats, Sprague-Dawley, Rotarod Performance Test.
- MESH :
- chemical , administration & dosage : DNA.
- chemical , chemistry : Polyethylene Glycols, Polylysine.
- chemical , genetics : Glial Cell Line-Derived Neurotrophic Factor.
- chemistry : Nanoparticles.
- cytology : Neurons.
- drug effects : Motor Activity.
- metabolism : Corpus Striatum, Dopamine, Glial Cell Line-Derived Neurotrophic Factor, Neurons, Plasmids.
- pathology : Corpus Striatum.
- therapy : Parkinson Disease.
- transplantation : Mesencephalon, Neurons.
- Animals, Behavior, Animal, Brain Tissue Transplantation, Disease Models, Animal, Fetal Tissue Transplantation, Gene Transfer Techniques, Male, Rats, Rats, Sprague-Dawley, Rotarod Performance Test.
Abstract
Previously it was established that infusion of glial cell line-derived neurotrophic factor (GDNF) protein into grafts of embryonic dopamine cells has a neurotrophic effect on the grafted cells. In this study we used a nonviral technique to transfer the gene encoding for GDNF to striatal cells. Plasmid DNA encoding for GDNF was compacted into DNA nanoparticles (DNPs) by 10 kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK(30)PEG10k) and then injected into the denervated striatum of rats with unilateral 6-hydroxydopamine lesions. Sham controls were injected with saline. One week later, experimental animals received either a ventral mesencephalic (VM) tissue chunk graft or a cell suspension VM graft implanted into the denervated striatum. Grafts were allowed to integrate for 4-6 weeks and during this period we monitored spontaneous and drug-induced motor activity. Using stereological cell counting we observed a 16-fold increase in the number of surviving TH(+) cells within tissue chunk grafts placed into the striatum pretreated with pGDNF DNPs (14,923 +/- 4,326) when compared to grafts placed into striatum pretreated with saline (955 +/- 343). Similarly, we observed a sevenfold increase in the number of TH(+) cells within cell suspension grafts placed into the striatum treated with pGDNF DNPs when compared to cell suspension grafts placed into the saline dosed striatum. Behaviorally, we observed significant improvement in rotational scores and in spontaneous forepaw usage of the affected forelimb in grafted animals receiving prior treatment with compacted pGDNF DNPs when compared to grafted animals receiving saline control pretreatment. Data analysis for protein, morphological, and behavioral measures suggests that compacted pGDNF DNPs injected into the striatum can result in transfected cells overexpressing GDNF protein at levels that provide neurotrophic support for grafted embryonic dopamine neurons.
DOI: 10.3727/096368909X12483162196881
PubMed: 19650971
Affiliations:
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Flectcher</name></author><author><name sortKey="Kowalczyk, Tomasz H" sort="Kowalczyk, Tomasz H" uniqKey="Kowalczyk T" first="Tomasz H" last="Kowalczyk">Tomasz H. Kowalczyk</name></author><author><name sortKey="Padegimas, Linas" sort="Padegimas, Linas" uniqKey="Padegimas L" first="Linas" last="Padegimas">Linas Padegimas</name></author><author><name sortKey="Cooper, Mark J" sort="Cooper, Mark J" uniqKey="Cooper M" first="Mark J" last="Cooper">Mark J. 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Yurek</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurosurgery, University of Kentucky College of Medicine, Lexington, KY 40536-0305, USA. David.Yurek@uky.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurosurgery, University of Kentucky College of Medicine, Lexington, KY 40536-0305</wicri:regionArea><placeName><region type="state">Kentucky</region></placeName></affiliation></author><author><name sortKey="Flectcher, Anita M" sort="Flectcher, Anita M" uniqKey="Flectcher A" first="Anita M" last="Flectcher">Anita M. Flectcher</name></author><author><name sortKey="Kowalczyk, Tomasz H" sort="Kowalczyk, Tomasz H" uniqKey="Kowalczyk T" first="Tomasz H" last="Kowalczyk">Tomasz H. 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(metabolism)</term><term>Neurons (transplantation)</term><term>Parkinson Disease (therapy)</term><term>Plasmids (metabolism)</term><term>Polyethylene Glycols (chemistry)</term><term>Polylysine (chemistry)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Rotarod Performance Test</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (administration et posologie)</term><term>Activité motrice ()</term><term>Animaux</term><term>Comportement animal</term><term>Corps strié (anatomopathologie)</term><term>Corps strié (métabolisme)</term><term>Dopamine (métabolisme)</term><term>Facteur neurotrophique dérivé des cellules gliales (génétique)</term><term>Facteur neurotrophique dérivé des cellules gliales (métabolisme)</term><term>Maladie de Parkinson ()</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Mésencéphale (transplantation)</term><term>Nanoparticules ()</term><term>Neurones (cytologie)</term><term>Neurones 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Sprague-Dawley</term><term>Rats</term><term>Techniques de transfert de gènes</term><term>Test du rotarod</term><term>Transplantation de tissu cérébral</term><term>Transplantation de tissu foetal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Previously it was established that infusion of glial cell line-derived neurotrophic factor (GDNF) protein into grafts of embryonic dopamine cells has a neurotrophic effect on the grafted cells. In this study we used a nonviral technique to transfer the gene encoding for GDNF to striatal cells. Plasmid DNA encoding for GDNF was compacted into DNA nanoparticles (DNPs) by 10 kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK(30)PEG10k) and then injected into the denervated striatum of rats with unilateral 6-hydroxydopamine lesions. Sham controls were injected with saline. One week later, experimental animals received either a ventral mesencephalic (VM) tissue chunk graft or a cell suspension VM graft implanted into the denervated striatum. Grafts were allowed to integrate for 4-6 weeks and during this period we monitored spontaneous and drug-induced motor activity. Using stereological cell counting we observed a 16-fold increase in the number of surviving TH(+) cells within tissue chunk grafts placed into the striatum pretreated with pGDNF DNPs (14,923 +/- 4,326) when compared to grafts placed into striatum pretreated with saline (955 +/- 343). Similarly, we observed a sevenfold increase in the number of TH(+) cells within cell suspension grafts placed into the striatum treated with pGDNF DNPs when compared to cell suspension grafts placed into the saline dosed striatum. Behaviorally, we observed significant improvement in rotational scores and in spontaneous forepaw usage of the affected forelimb in grafted animals receiving prior treatment with compacted pGDNF DNPs when compared to grafted animals receiving saline control pretreatment. Data analysis for protein, morphological, and behavioral measures suggests that compacted pGDNF DNPs injected into the striatum can result in transfected cells overexpressing GDNF protein at levels that provide neurotrophic support for grafted embryonic dopamine neurons.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Kentucky</li></region></list><tree><noCountry><name sortKey="Cooper, Mark J" sort="Cooper, Mark J" uniqKey="Cooper M" first="Mark J" last="Cooper">Mark J. Cooper</name><name sortKey="Flectcher, Anita M" sort="Flectcher, Anita M" uniqKey="Flectcher A" first="Anita M" last="Flectcher">Anita M. Flectcher</name><name sortKey="Kowalczyk, Tomasz H" sort="Kowalczyk, Tomasz H" uniqKey="Kowalczyk T" first="Tomasz H" last="Kowalczyk">Tomasz H. Kowalczyk</name><name sortKey="Padegimas, Linas" sort="Padegimas, Linas" uniqKey="Padegimas L" first="Linas" last="Padegimas">Linas Padegimas</name></noCountry><country name="États-Unis"><region name="Kentucky"><name sortKey="Yurek, David M" sort="Yurek, David M" uniqKey="Yurek D" first="David M" last="Yurek">David M. Yurek</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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