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  Loss of microglial ramification in microglia-astrocyte cocultures: Involvement of adenylate cyclase, calcium, phosphatase, and G(i)-protein systems

Kalla, R., Bohatschek, M., Kloss, C. U. A., Krol, J., von Maltzan, X., & Raivich, G. (2003). Loss of microglial ramification in microglia-astrocyte cocultures: Involvement of adenylate cyclase, calcium, phosphatase, and G(i)-protein systems. Glia, 41(1), 50-63. doi:10.1002/glia.10176.

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Kalla, R.1, Author           
Bohatschek, M.1, Author           
Kloss, C. U. A.1, Author           
Krol, J.2, Author
von Maltzan, X.2, Author
Raivich, G.1, Author           
Affiliations:
1Emeritus Group: Neuromorphology / Kreutzberg, MPI of Neurobiology, Max Planck Society, ou_1113551              
2Univ Coll London, Perinatal Brain Grp, Dept Obstet & Gynaecol, Dept Anat, London WC1E 6HX, England.; Max Planck Inst Neurobiol, Dept Neuromorphol, Martinsried, Germany., ou_persistent22              

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 Abstract: Reduction in microglial branching is a common feature in brain pathology and culminates in the transformation into small, rounded, microglia-derived phagocytes in the presence of neural debris. The molecular factors responsible for this transformation are unknown. Here we explored the effect of different classes of intra- and extracellular stimuli in vitro on the morphology of ramified microglia cultured on a confluent astrocyte substrate. These studies showed a strong dose-dependent effect for the Ca2+ ionophore calcimycine/A21837 (50 muM) and for dibutyryl-cAMP (1 mM), with a loss of microglial ramification. Direct activation of the adenylate cyclase with forskolin (0.1 mM) also led to the disappearance of microglial branching. Okadaic acid (70 nM), the inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), and pertussis toxin (12.5 mug/ml), a G(i)-protein inhibitor, also showed similar effects. No effect was observed for dibutyryl-cGMP or for UTP; addition of ATP had a moderate effect, but only at very high, probably nonphysiological concentrations (100 mM). Extracellular matrix components such as keratatan-sulfate, integrin receptor blockers, the disintegrins kistrin, echistatin, and flavoridin, or the serine protease thrombin all had no effect. Addition of prostaglandin D-2 (PGD(2)), a molecule produced by activated microglial cells, had a transforming effect, but at concentrations two orders of magnitude higher than that of established PGD(2) receptors. In summary, addition of agents causing intracellular elevation of Ca2+ and cAMP or inhibition of G(i)-proteins and phosphatases to ramified microglia cultured on top of confluent astrocytes leads to a rapid loss of microglial branching. Signaling cascades controlled by these molecules may play an important role in the regulation of this common physiological process in the injured brain. (C) 2003 Wiley-Liss, Inc.

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Language(s): eng - English
 Dates: 2003-01
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 127681
ISI: 000180158400006
DOI: 10.1002/glia.10176
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Title: Glia
  Other : Glia
Source Genre: Journal
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Publ. Info: New York, N.Y. : Wiley-Liss, Inc.
Pages: - Volume / Issue: 41 (1) Sequence Number: - Start / End Page: 50 - 63 Identifier: ISSN: 0894-1491
CoNE: https://pure.mpg.de/cone/journals/resource/954925558509