Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats.
Recently we showed that the neurotensin polyplex is a nanoparticle carrier system that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report its first practical application in experimental parkinsonism, which consisted of transfecting dopamine neurons with the gene coding for human glial cell line-derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the striatum. We showed that transfection of the hGDNF gene into the substantia nigra of rats 1 week after the neurotoxin injection produced biochemical, anatomical, and functional recovery from hemiparkinsonism. RT-PCR analysis showed mRNA expression of exogenous hGDNF in the transfected substantia nigra. Western blot analysis verified transgene expression by recognizing the flag epitope added at the C-terminus of the hGDNF polypeptide, which was found mainly in dopamine neurons by double immunofluorescence techniques. These data indicate that the neurotensin polyplex holds great promise for the neuroprotective therapy of Parkinson disease.
Gonzalez-Barrios
Juan A
JA
Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Apdo. Postal 14-740, 07000 México, D.F., México.
Lindahl
Maria
M
Bannon
Michael J
MJ
Anaya-Martínez
Veronica
V
Flores
Gonzalo
G
Navarro-Quiroga
Ivan
I
Trudeau
Louis E
LE
Aceves
Jorge
J
Martinez-Arguelles
Daniel B
DB
Garcia-Villegas
Refugio
R
Jiménez
Ismael
I
Segovia
Jose
J
Martinez-Fong
Daniel
D
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008694:Methamphetamine / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000737:chemistry*; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009496:Neurotensin; D008694:Methamphetamine; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine