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GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro.

Authors
Park, JY; Kim, HY; Jou, I; Park, SM
Citation
Brain research, 124413-23, 2008
Journal Title
Brain research
ISSN
0006-89931872-6240
Abstract
Microglia are immunologically competent cells in the central nervous system and considered to be a key player in brain inflammation. The morphological change of microglia has been shown to be linked to functional phenotypes both in vivo and in vitro. As an attempt to identify factors that regulate microglial morphology, we investigated the effect of gangliosides on microglial ramification in vitro. Brain gangliosides mixture and GM1 induced typical ramification of cultured rat primary microglia, however, GD1a and GT1b did not. Although GM1 significantly induced the expression of neurotrophin-3 (NT-3), NT-3 did not induce typical morphological changes in cultured rat primary microglia. SB203580 (an inhibitor of p38), and paclitaxel and nocodazole (microtubule-disrupting drugs) inhibited GM1-induced microglial ramification, but Jaki (an inhibitor of JAK), PD98059 (an inhibitor of Erk1/2), SP600125 (an inhibitor of JNK), and cytochalasin B and latrunculin B (actin polymerization inhibitors) did not, suggesting that GM1 induced ramification of microglia in p38- and microtubule-dependent manner. This in vitro system would be helpful in understanding the mechanisms of microglial ramification and physiological roles of gangliosides in microglia.
MeSH terms
AnimalsBlotting, WesternCell Differentiation/drug effects*Cells, CulturedDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayG(M1) Ganglioside/pharmacology*Gangliosides/pharmacologyImidazoles/pharmacologyInterferon-gamma/pharmacologyLipopolysaccharides/pharmacologyMicroglia/cytologyMicroglia/drug effects*Microglia/metabolismMicroscopy, ConfocalMicrotubules/drug effects*Microtubules/metabolismNerve Growth Factor/geneticsNerve Growth Factor/metabolismNeurotrophin 3/geneticsNeurotrophin 3/metabolismNeurotrophin 3/pharmacologyNocodazole/pharmacologyPaclitaxel/pharmacologyPyridines/pharmacologyRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionTubulin Modulators/pharmacologyp38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsp38 Mitogen-Activated Protein Kinases/metabolism*
DOI
10.1016/j.brainres.2008.09.072
PMID
18930716
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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