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Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer's disease
Author(s) -
Yi Chenju,
Ezan Pascal,
Fernández Paola,
Schmitt Julien,
Sáez Juan C.,
Giaume Christian,
Koulakoff Annette
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23182
Subject(s) - neuroscience , microglia , biology , gliosis , neuroprotection , hippocampal formation , connexin , astrogliosis , glutamate receptor , context (archaeology) , astrocyte , central nervous system , gap junction , microbiology and biotechnology , intracellular , immunology , inflammation , receptor , biochemistry , paleontology
The contribution of reactive gliosis to the pathological phenotype of Alzheimer's disease (AD) opened the way for therapeutic strategies targeting glial cells instead of neurons. In such context, connexin hemichannels were proposed recently as potential targets since neuronal suffering is alleviated when connexin expression is genetically suppressed in astrocytes of a murine model of AD. Here, we show that boldine, an alkaloid from the boldo tree, inhibited hemichannel activity in astrocytes and microglia without affecting gap junctional communication in culture and acute hippocampal slices. Long‐term oral administration of boldine in AD mice prevented the increase in glial hemichannel activity, astrocytic Ca 2+ signal, ATP and glutamate release and alleviated hippocampal neuronal suffering. These findings highlight the important pathological role of hemichannels in AD mice. The neuroprotective effect of boldine treatment might provide the basis for future pharmacological strategies that target glial hemichannels to reduce neuronal damage in neurodegenerative diseases.