Faculty Collaboration Database

Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease. Exp Neurol 2008 Jan;209(1):213-23

Date

12/07/2007

Pubmed ID

18061591

DOI

10.1016/j.expneurol.2007.09.022

Scopus ID

2-s2.0-37549042851 (requires institutional sign-in at Scopus site)   130 Citations

Abstract

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.

Author List

Ebert AD, Beres AJ, Barber AE, Svendsen CN

Author

Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amphetamine
Animals
Cell Differentiation
Cells, Cultured
Central Nervous System Stimulants
Data Interpretation, Statistical
Dopamine
Enzyme-Linked Immunosorbent Assay
Glial Cell Line-Derived Neurotrophic Factor
Humans
Immunohistochemistry
Insulin-Like Growth Factor I
Lentivirus
Male
Nerve Fibers
Neurons
Oxidopamine
Parkinson Disease, Secondary
Rats
Rats, Inbred Lew
Stem Cell Transplantation
Stem Cells
Stereotyped Behavior
Sympatholytics
Tyrosine 3-Monooxygenase