Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 45, Issue 1, Pages 37-46Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2010.05.007
Keywords
Astrocytes; Connexins; Neuro-inflammation; Excitotoxicity; Neuroprotection
Categories
Funding
- INSERM/CONICYT
- CRPCEN (France)
- FONDECYT [1070591]
- Heart & Stroke Foundation of BC Yukon
- Heart & Stroke Foundation
- France Alzheimer (France)
- College de France (Paris)
- INSERM (Departement des Relations Internationales)
- Canadian Institutes of Health Research-Vancouver Coastal Health Research Institute-UBC
- Michael Smith Foundation for Health Research
Ask authors/readers for more resources
Astrocytes express high levels of connexin43, a protein that forms two types of channels: gap junction channels for direct intercellular communication, and hemichannels for exchanges with the extracellular space. Inflammation induces connexin43 hemichannel activation, which has been proposed to be involved in neuroglial interactions. Here, we investigated the contribution of connexin43 to NMDA-induced excitotoxicity in neuron/astrocyte cocultures, after treatment with a pro-inflammatory cytokine mixture, containing TNF-alpha and IL1-beta (Mix), that stimulated astroglial connexin43 hemichannel activity. Interestingly, NMDA treatment induced a higher amount of neurotoxicity in Mix-treated co-cultures than in untreated ones, whereas this extent of neurotoxicity was absent in enriched neuron cultures or in co-cultures with connexin43 knock-out astrocytes. Furthemore, application of connexin43 hemichannel blockers or a synthetic cannabinoid prevented the Mix-induced potentiated NMDA neurotoxicity. Altogether, these data demonstrate that inflammation-induced astroglial hemichannel activation plays a critical role in neuronal death and suggest a neuroprotective role of connexin43 hemichannel blockade. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available