The change of the neuron-glia differentiation rate in human neural precursor cells (HPCs) and Ad-BDNF-/-GDNF-infected HPCs following the administration of a neurotoxin.
Neurotrophic factors promote the survival of various neurons, including peripheral autonomic and sensory neurons, as well as central motor and dopamine neurons, and it is expected that they could function as therapeutic agents for neurodegenerative disease. We examined the changes in the neuron-glia differentiation rate in normal human neural precursor cells (HPCs), Ad-BDNF- and Ad-GDNF-infected HPCs following their treatment with 6-OHDA. We isolated the precursor cells from the human fetal midbrain. To investigate the expression of differentiated cell markers within neurons and glia after 6-OHDA-induced toxicity in HPCs, immunocytochemistry was performed. Our results showed that the treatment with 6-OHDA (100, 200, 300, 400 and 500 microM) for 24 h decreased the viability of the HPCs in vitro. Among the growth factors tested, BDNF and GDNF protected the HPCs against 6-OHDA-induced toxicity. Approximately, 5.8+/-2.2% and 0.5+/-0.1% of the HPCs treated with 6-OHDA were positive for the neuron marker, MAP2, and the oligodendrocyte marker, GalC, respectively, while 13.8+/-3.2% and 1.1+/-0.36% of the Ad-BDNF- or Ad-GDNF-infected HPCs treated with 6-OHDA stained positive for MAP2 and GalC, respectively. These results suggest that cocktail therapy using human precursor cells (HPCs) and certain neurotrophic factors (BDNF, GDNF) provide direct protection against 6-OHDA-induced toxicity and has an effect on the differentiation rate.
Yoo
Young Mi
YM
Department of Neurosurgery, Gachon Medical College, Gil Medical Center, 1198 Kuwel-Dong, Namdong-Ku, Incheon 405-220, South Korea. neurobeauty@hanmail.net
Kim
Yong Jung
YJ
Lee
Uhn
U
D000256:Adenoviridae / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013565:Sympatholytics / Q000633:toxicity; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D013565:Sympatholytics; D016627:Oxidopamine