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Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression

Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression Thumbnail


Abstract

During development a tightly controlled signaling cascade dictates the differentiation, maturation and survival of developing neurons. Understanding this signaling mechanism is important for developing therapies for neurodegenerative illnesses. In previous work we have sought to understand the complex signaling pathways responsible for the development of midbrain dopamine neurons using a proteomic approach. One protein we have identified as being expressed in developing midbrain tissue is the vitamin D receptor. Therefore we investigated the effect of the biologically active vitamin D3 metabolite, calcitriol, on primary fetal ventral mesencephalic cultures of dopamine neurons. We observed a dose responsive increase in numbers of rat primary dopamine neurons when calcitriol was added to culture media. Western blot data showed that calcitriol upregulated the expression of glial derived neurotrophic factor (GDNF). Blocking GDNF signaling could prevent calcitriol's ability to increase numbers of dopamine neurons. An apoptosis assay and cell birth dating experiment revealed that calcitriol increases the number of dopamine neurons through neuroprotection and not increased differentiation. This could have implications for future neuroprotective PD therapies.

Citation

(2013). Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression. PloS one, e62040 -?. https://doi.org/10.1371/journal.pone.0062040

Acceptance Date Mar 18, 2013
Publication Date Apr 23, 2013
Journal PloS one
Print ISSN 1932-6203
Publisher Public Library of Science
Pages e62040 -?
DOI https://doi.org/10.1371/journal.pone.0062040
Keywords calcitriol, neuroprotection, midbrain dopaminergic neurons

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