Abstract
Growth factors play a crucial role during de- and remyelination of the central nervous system (CNS) due to their neurotrophic functions. We have previously shown that the growth factors neuregulin-1 (Nrg-1) and glial cell-derived neurotrophic factor (Gdnf) are upregulated during the first 2 weeks after induction of toxic demyelination in the CNS. Nevertheless, the factors responsible for Nrg-1/Gdnf upregulation and their effects on glia cells are unknown. We investigated the effect on Nrg-1 and Gdnf expressions after stimulation of primary mouse microglia or astrocytes with various pro- and anti-inflammatory factors. Additionally, primary cells were incubated with NRG-1 and/or GDNF followed by determining the gene expression level of their receptors, chemokines, and other growth factors. We demonstrate that inflammatory stimuli have a distinct impact on the expression of Gdnf, Nrg-1, and their receptors in astrocytes and microglia. In microglia, LPS or simultaneous treatment with IFNγ plus TNFα led to downregulation of Nrg-1, whereas LPS treatment slightly increased Nrg-1 expression in astrocytes. Furthermore, Gdnf was slightly upregulated after TFG-β treatment in microglia, while Gdnf was significantly upregulated after LPS treatment in astrocytes. In contrast, treatment with GDNF or/and NRG-1 did not alter any measured gene expression in microglia or astrocytes. Taken together, our in vitro studies show that Nrg-1, Gdnf, and their receptors are differently regulated in astrocytes and microglia upon inflammatory stimuli. The lack of response of astrocytes and microglia to NRG-1 and GDNF suggests that both factors exert their effects directly on neurons.
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05 April 2019
The original version of this article unfortunately contained mistakes in the author group and affiliation sections. Author Markus H. Schwab’s name was incorrectly presented as “H. Markus Schwab” and his affiliations were incorrectly assigned as “1 and 3” instead of “2 and 3”.
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The authors thank I. Cierpka-Leja and S. Lang for excellent technical assistance.
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M.H. Schwab holds a Heisenberg Fellowship from Deutsche Forschungsgemeinschaft (DFG) and received funding by a DFG research grant (SCHW741/4-1).
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Kronenberg, J., Merkel, L., Heckers, S. et al. Investigation of Neuregulin-1 and Glial Cell-Derived Neurotrophic Factor in Rodent Astrocytes and Microglia. J Mol Neurosci 67, 484–493 (2019). https://doi.org/10.1007/s12031-019-1258-8
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DOI: https://doi.org/10.1007/s12031-019-1258-8