Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF. Neurobiol Dis 2009 Nov;36(2):303-11
Date
08/08/2009Pubmed ID
19660547Pubmed Central ID
PMC2989601DOI
10.1016/j.nbd.2009.07.022Scopus ID
2-s2.0-70349762432 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels.
Author List
Emborg ME, Moirano J, Raschke J, Bondarenko V, Zufferey R, Peng S, Ebert AD, Joers V, Roitberg B, Holden JE, Koprich J, Lipton J, Kordower JH, Aebischer PAuthor
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age FactorsAging
Animals
Corpus Striatum
Disease Models, Animal
Gene Transfer Techniques
Genetic Vectors
Glial Cell Line-Derived Neurotrophic Factor
Lentivirus
Macaca mulatta
Male
Parkinsonian Disorders
Psychomotor Performance
Recovery of Function
