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

Shohreh Majd, Arthur Smardencas, Clare Parish, John Drago

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)967-977
    Number of pages11
    JournalNeurochemical Research
    Volume36
    Issue number6
    DOIs
    Publication statusPublished - Jun 2011

    Keywords

    • Culture
    • Dopaminergic neuron
    • Midbrain
    • Neurotrophic factor
    • Tyrosine hydroxylase

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