Development of an In Vitro Model to Evaluate the Regenerative Capacity of Adult Brain-Derived Tyrosine Hydroxylase-Expressing Dopaminergic Neurons

The loss of nigral dopaminergic (DA) neurons is the disease-defining pathological change responsible for progressive motor dysfunction in Parkinson’s disease. In this study, we sought to establish a culture method for adult rat tyrosine hydroxylase (TH)-immunoreactive DA neurons. In this context, we...

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Bibliographic Details
Published in:Neurochemical research 2011-06, Vol.36 (6), p.967-977
Main Authors: Majd, Shohreh, Smardencas, Arthur, Parish, Clare L., Drago, John
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Brain - cytology
Brain - enzymology
Brain - metabolism
Cell Biology
Dopamine - metabolism
Female
In Vitro Techniques
Neurochemistry
Neurology
Neurons - enzymology
Neurons - metabolism
Neurosciences
Original Paper
Rats
Rats, Sprague-Dawley
Regeneration
Tyrosine 3-Monooxygenase - metabolism
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Summary:The loss of nigral dopaminergic (DA) neurons is the disease-defining pathological change responsible for progressive motor dysfunction in Parkinson’s disease. In this study, we sought to establish a culture method for adult rat tyrosine hydroxylase (TH)-immunoreactive DA neurons. In this context, we investigated the role of fibroblast growth factor 2 (FGF2), brain-derived neurotrophic factor (BDNF), transforming growth factor-β3 (TGF-β3), glial-derived neurotrophic factor (GDNF) and dibutyryl-cyclic AMP (dbcAMP) in these cultures. Culturing in the presence of FGF2, BDNF and GDNF enhanced the survival of DA neurons by 15-fold and promoted neurite growth. In contrast, dbcAMP promoted neurite growth in all neurons but did not enhance DA cell survival. This study demonstrates that long-term cultures of DA neurons can be established from the mature rat brain and that survival and regeneration of DA neurons can be manipulated by epigenetic factors such as growth factors and intracellular cAMP pathways.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-011-0435-0