Abstract
In this study, we investigated whether the increase of inhibitory gamma-amino butyric acid (GABA) signal suppresses the excitatory glutamate signal induced by cerebral ischemia and the underlying mechanisms. In global cerebral ischemia, focal cerebral ischemia and oxygen-glucose deprivation, application of muscimol and baclofen, agonists of GABA(A) receptor and GABA(B) receptor, exerted neuroprotection. The agonists inhibited the increased assembly of the GluR6-PSD-95-MLK3 module induced by cerebral ischemia and the activation of the MLK3-MKK4/7-JNK3 cascade. Our results suggest that stimulation of the inhibitory GABA receptors can attenuate the excitatory JNK3 apoptotic signaling pathway via inhibiting the increased assembly of the GluR6-PSD-95-MLK3 signaling module in cerebral ischemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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Baclofen / pharmacology
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Brain Ischemia / metabolism*
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Disks Large Homolog 4 Protein
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GABA Agonists / pharmacology
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GluK2 Kainate Receptor
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Immunohistochemistry
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Intracellular Signaling Peptides and Proteins / metabolism*
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MAP Kinase Kinase Kinases / metabolism*
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Male
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Membrane Proteins / metabolism*
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Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase Kinase Kinase 11
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Muscimol / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, GABA / metabolism*
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Receptors, Kainic Acid / metabolism*
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Reperfusion Injury / metabolism*
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Signal Transduction*
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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GABA Agonists
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Receptors, GABA
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Receptors, Kainic Acid
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Muscimol
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Mitogen-Activated Protein Kinase 10
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MAP Kinase Kinase Kinases
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Baclofen