Functions of connexins and large pore channels on microglial cells: The gates to environment

Department of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, D-44780 Bochum, Germany.
Brain research (Impact Factor: 2.83). 07/2012; 1487. DOI: 10.1016/j.brainres.2012.07.020
Source: PubMed

ABSTRACT Microglial cells are not only sensitive indicators for pathology of the central nervous system (CNS), they are a key factor for neurotoxicity and degeneration in many diseases. Neuronal damage leads to reactive gliosis and to activation of microglia including cytoarchitectonic changes accompanied by alterations in surface receptor and channel expression. In this context, the release of neuroactive soluble factors like pro-inflammatory cytokines can result in increased cellular motility and a higher grade of phagocytotic activity. Ligands including glutamate, tumor necrosis factor alpha (TNF-α), cytokines, superoxide radicals and neurotrophins released by microglia have in turn effects on neuronal function and cell death. The current review focuses on large pore and hemichannel function in microglial cells under different conditions of activation and elucidates the role of these channels in cytokine release, as well as putative targets for clinical intervention in case of inflammatory processes. This article is part of a Special Issue entitled Electrical Synapses.

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    • "Consistently, non-vesicular secretory mechanisms in microglia have been indicated as putative gates for excessive transmitter release in pathological conditions, as in the case of neurotoxic glutamate release through connexin hemichannels in the Rett syndrome (Maezawa and Jin, 2010). While recent reviews have comprehensively described alterations of non-vesicular secretory paths in relation to the activation state of microglia and have proposed non secretory mechanisms as putative targets for clinical intervention in brain diseases (Kielian, 2008; Mika and Prochnow, 2012), vesicular secretory pathways operating in microglia have been poorly investigated and reviewed. Hence, we here focus on emerging evidence indicating the coexistence in microglia of both classical, regulated secretion, and unconventional vesicular secretory mechanisms, the latter consisting in the release of extracellular membrane microvesicles (EMVs). "
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