A neuroprotective role for gap junctions.
Glial-neuronal interactions have been implicated in both normal information processing and neuroprotection. One pathway of cellular interactions involves gap junctional intercellular communication (GJIC). In astrocytes, gap junctions are composed primarily of the channel protein, connexin43 (Cx43), and provide a substrate for formation of a functional syncytium implicated in the process of spatial buffering in the CNS. Thus gap junctional communication may be neuroprotective following a CNS insult that entails glutamate cytotoxicity (i.e. ischemia). We have shown that blocking gap junctions during a glutamate insult to co-cultures of astrocytes and neurons results in increased neuronal injury. To assess the effect of reduced Cx43 and GJIC on neuroprotection, we examined brain infarct volume in wild type and Cx43 heterozygote null mice following focal ischemia. Cx43 heterozygous null mice exhibited a significantly larger infarct volume compared to wild type. At the cellular level, a significant increase in TUNEL positive cells was observed in the penumbral region of the Cx43 heterozygote mice. These results suggest that augmentation of GJIC in astrocytes may contribute to neuroprotection following ischemic injury. These findings support the hypothesis that gap junctions play a neuroprotective role against glutamate cytotoxicity.
Naus
C C
CC
Department of Anatomy & Cell Biology, The University of Western Ontario, London, Canada. cnaus@uwo.ca
Ozog
M A
MA
Bechberger
J F
JF
Nakase
T
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018031:Connexin 43; D018698:Glutamic Acid; D002229:Carbenoxolone