Protection of cultured dopamine neurons from MPP+ requires a combination of neurotrophic factors

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• 作者：Juliann D. Jaumotte ; Stephanie L. Wyrostek and Michael J. Zigmond
• 刊名：European Journal of Neuroscience
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：44
• 期：1
• 页码：1691-1699
• 全文大小：2167K
• ISSN：1460-9568

文摘

Parkinson's disease is a progressive neurodegenerative disorder, caused in part by the loss of dopamine (DA) neurons in the substantia nigra (SN). Neurotrophic factors have been shown to increase the basal survival of DA neurons in vitro, as well as to protect the neurons from some toxins under certain in vitro conditions and in animal models. Although these factors have often been tested individually, they have rarely been studied in combinations. We therefore examined the effect of such combinations after acute exposure to the toxin 1-methyl-4-phenylpyridinium (MPP⁺) using dissociated postnatal rat midbrain cultures isolated from SN and ventral tegmental area (VTA). We found that significant loss of DA neurons in the SN occurred with an LC₅₀ of between 1 and 10 μm, whereas the LC₅₀ of DA neurons from the VTA was approximately 1000-fold higher. We did not observe neuroprotection against MPP⁺ by individual exposure to glial cell-line derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), transforming growth factor beta (TGFβ), basic fibroblast growth factor (FGF-2) or growth/differentiation factor 5 (GDF5) at concentrations of 100 or 500 ng/mL. Combinations of two, three or four neurotrophic factors were also ineffective. However, when the SN cultures were exposed to a combination of all five neurotrophic factors, each at a concentration of 100 ng/mL, we observed a 30% increase in DA neuron survival in the presence of 10 and 500 μm MPP⁺. These results may be relevant to the use of neurotrophic factors as therapeutic treatments for Parkinson's disease.