Establishment of a Survival and Toxic Cellular Model for Parkinson’s Disease from Chicken Mesencephalon

Amparo Tolosa,Xiaolai Zhou,Kerstin Krieglstein,Björn Spittau

doi:10.1007/s12640-012-9367-y

Amparo Tolosa, Xiaolai Zhou + Show 2 more

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https://doi.org/10.1007/s12640-012-9367-y

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Journal: Neurotoxicity research	Publication Date: Dec 13, 2012
Citations: 25	License type: cc-by

Affiliation: University of Freiburg

Abstract

Cellular models for Parkinson’s disease (PD) represent a fast and efficient tool in the screening for drug candidates and factors involved in the disease pathogenesis. The objective of this study was to establish and characterize a survival and toxic cellular model for PD by culturing dopaminergic neurons from embryonic chicken ventral midbrain. We show that as in rodents, the common neurotrophic factors—brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2)—are able to support the survival of chicken midbrain dopaminergic neurons. Furthermore, after treatment with MPP+ or rotenone as in vitro models for PD, the number of tyrosine hydroxylase-positive cells decreased drastically. This effect could be significantly rescued by treatment with BDNF or GDNF. Together, our results indicate that mechanisms of neuroprotection of dopaminergic neurons are conserved between chicken and mammals. This supports the use of primary culture from chicken embryonic midbrain as a suitable tool for the study of neuroprotection in vitro.

Highlights

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders of the central nervous system
We show that as in rodents, the common neurotrophic factors—brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2)—are able to support the survival of chicken midbrain dopaminergic neurons
We provide evidence that as in rodents, the common neurotrophic factors brainderived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2) are able to support the survival of chicken midbrain dopaminergic neurons

Summary

Introduction

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders of the central nervous system. The use of neurotrophic factors represents a potential therapeutic strategy, to increase the survival of the remaining DA neurons and to support those transplanted (Poewe 2006; Schapira 2009) Within this context, different neurotrophic factors such as neurotrophin, fibroblast growth factor (FGF), epidermal growth factor (EGF), ciliary neurotrophic factor (CNTF), insulin-like growth factor (IGF), transforming growth factor-beta (TGF-b), and interleukin families have been identified to promote survival of DA neurons (von Bohlen und Halbach and Unsicker 2009). Different neurotrophic factors such as neurotrophin, fibroblast growth factor (FGF), epidermal growth factor (EGF), ciliary neurotrophic factor (CNTF), insulin-like growth factor (IGF), transforming growth factor-beta (TGF-b), and interleukin families have been identified to promote survival of DA neurons (von Bohlen und Halbach and Unsicker 2009) Several of these factors have been tested using both, animal and cellular systems, Neurotox Res (2013) 24:119–129 providing evidence that the two approaches are robust and contribute to a better understanding of the disease. Advantages of the cellular models for PD are the rapid screening for drug candidates or factors involved in disease pathogenesis and the consequent decrease in the necessary number of animal experiments

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