Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in vitro.
Glial cell line-derived neurotrophic factor (GDNF) is known as a potent neurotrophic factor for dopaminergic neurons. Since adeno-associated virus (AAV) vector is a suitable vehicle for gene transfer into neurons, rat E14 mesencephalic cells were transduced with an AAV vector expressing GDNF. When compared with mock transduction, a larger number of dopaminergic neurons survived in AAV-GDNF-transduced cultures (234% and 325% of controls at 1 and 2 weeks, respectively; P < 0.01). Furthermore, the dopaminergic neurons in the latter cultures grew more prominent neurites than those in the former. These findings suggest that AAV vector-mediated GDNF gene transfer may prevent dopaminergic neuron death, and is therefore a logical approach for the treatment of Parkinson's disease.
Fan
D
D
Department of Neurology, Jichi Medical School, Tochigi, Japan.
Ogawa
M
M
Ikeguchi
K
K
Fujimoto
K
K
Urabe
M
M
Kume
A
A
Nishizawa
M
M
Matsushita
N
N
Kiuchi
K
K
Ichinose
H
H
Nagatsu
T
T
Kurtzman
G J
GJ
Nakano
I
I
Ozawa
K
K
D000818:Animals; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics*; D004298:Dopamine / Q000502:physiology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine