Clinical NeuroscienceResearch PaperNeuroprotection of ethanol against ischemia/reperfusion-induced brain injury through decreasing c-Jun N-terminal kinase 3 (JNK3) activation by enhancing GABA release
Section snippets
Antibodies and reagents
The following primary antibodies from Santa Cruz Biotechnology (Santa Cruz, CA, USA) were used: rabbit polyclonal anti-MLK3 (sc-13072), monoclonal anti-phospho-JNKs (sc-6254), monoclonal anti-JNK3, rabbit polyclonal anti-Fas-L (sc-6237), and rabbit polyclonal anti-c-Jun (sc-9164). Rabbit polyclonal anti-phospho-MLK3, anti-p-MKK7 (No. 4172), and anti-MKK7 (No. 4171) were obtained from Cell Signaling Biotechnology (Santa Cruz, CA, USA). Rabbit polyclonal anti-Gluk2 antibody (catalog No. 06-309)
Neuroprotective effects of ethanol against cerebral ischemia/reperfusion-induced apoptotic neuronal death in hippocampal CA1 neurons
To probe whether ethanol has neuroprotective effect against ischemic injury, we investigated the effects of ethanol on the neuronal survival of CA1 pyramidal neurons in rat hippocampus after 5 days of reperfusion. Cresyl Violet staining was used to examine the surviving cells in the CA1 region. Normal cells show round and pale-stained nuclei. The shrunken cells with pyknotic nuclei after reperfusion were counted as dead cells. Transient cerebral ischemia (15 minutes) followed by 5 days of
Discussion
In this study we reported for the first time that ethanol has a neuroprotective effect against ischemic brain injury by enhancing GABA release and decreasing JNK3 activation via suppression of the assembly of signaling module Gluk2–PSD-95–MLK3. Our experimental results indicate that ethanol has neuroprotective effects against ischemic brain injury in vivo (Fig. 1) through suppressing the phosphorylation of MLK3/MKK4/7/JNK3/c-Jun and the expression of Fas-L (Fig. 5, Fig. 6A, B). However, as an
Acknowledgments
Support was provided by the Great Research Project of the National Nature Science Foundation of China (grant 90608015), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (grants 08KJB180010 and 07KJA18030), and the Research Project of the National Youth Science Foundation of China (grant 30700117).
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S.-H. Qi and Y. Liu contributed equally to this work.