Correction to: Investigation of Neuregulin-1 and Glial Cell-Derived Neurotrophic Factor in Rodent Astrocytes and Microglia.

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".

Polarized microglia do not influence oligodendrocyte lineage cells via astrocytes.

Microglia can adopt different activation patterns, ranging from a pro-inflammatory M1- to an anti-inflammatory M2-like phenotype in which they play crucial roles in various neuroinflammatory diseases. M2-like microglia are described to drive remyelination, whereas detrimental effects have been attributed to M1-like microglia. How polarized microglia might act on oligodendrocyte lineage cells indirectly by influencing astrocytes has not been studied in detail. In this study, conditioned media from polarized murine microglia were used to treat astrocytes and astrocytic gene expression was analyzed by microarray for genes known to influence oligodendrocyte lineage cells. Supernatants of astrocytes previously stimulated with soluble effectors from polarized microglia were used to investigate effects on oligodendrocyte precursor cells (OPC). Growth factors known to induce OPC proliferation, differentiation, and survival were upregulated in astrocytes treated with supernatants from M1-like microglia while M0- and M2-like microglia only had negligible effects on the expression of these factors in astrocytes. Despite the upregulation of these factors in M1 stimulated astrocytes there were no significant effects on OPC in vitro. All astrocyte supernatants induced proliferation of A2B5+ OPC and inhibited differentiation of OPC into mature oligodendrocytes. A trend toward enhanced migration of OPC was induced by M1 stimulated astrocytes. Our data suggest that M1-like microglia may potentially influence OPC and remyelination indirectly via astrocytes by inducing the expression of respective growth factors, however, this has no significant effect in addition to the already strong effects of unstimulated astrocytes on OPC. Nevertheless, the observed effect may be of relevance in other pathophysiological scenarios.

Investigation of Neuregulin-1 and Glial Cell-Derived Neurotrophic Factor in Rodent Astrocytes and Microglia.

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-ß 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.