Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease.
Growth factors such as glial cell line-derived neurotrophic factor (GDNF) have been shown to prevent neurodegeneration and promote regeneration in many animal models of Parkinson's disease (PD). Insulin-like growth factor 1 (IGF-1) is also known to have neuroprotective effects in a number of disease models but has not been extensively studied in models of PD. We produced human neural progenitor cells (hNPC) releasing either GDNF or IGF-1 and transplanted them into a rat model of PD. hNPC secreting either GDNF or IGF-1 were shown to significantly reduce amphetamine-induced rotational asymmetry and dopamine neuron loss when transplanted 7 days after a 6-hydroxydopamine (6-OHDA) lesion. Neither untransduced hNPC nor a sham transplant had this effect suggesting GDNF and IGF-1 release was required. Interestingly, GDNF, but not IGF-1, was able to protect or regenerate tyrosine hydroxylase-positive fibers in the striatum. In contrast, IGF-1, but not GDNF, significantly increased the overall survival of hNPC both in vitro and following transplantation. This suggests a dual role of IGF-1 to both increase hNPC survival after transplantation and exert trophic effects on degenerating dopamine neurons in this rat model of PD.
Ebert
Allison D
AD
The Waisman Center and Department of Anatomy, University of Wisconsin Madison, Madison, WI 53705-2280, USA. ebert@waisman.wisc.edu
Beres
Amy J
AJ
Barber
Amelia E
AE
Svendsen
Clive N
CN
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000494:pharmacology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009412:Nerve Fibers / Q000201:enzymology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000697:Central Nervous System Stimulants; D051100:Glial Cell Line-Derived Neurotrophic Factor; D013565:Sympatholytics; D007334:Insulin-Like Growth Factor I; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine