Premium
Activation of GABA¬A receptor Protects Mitochondria and Reduces Cerebral ischemia.
Author(s) -
Tyagi Neetu,
Givvimani Srikanth,
Kumar Munish,
Kundu Soumi,
Gillespie William M,
Mishra Paras,
Sathnur Pushpa Kumar,
Lominadze David,
Sen Utpal,
Tyagi Suresh C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.614.8
Subject(s) - neuroprotection , mitochondrial permeability transition pore , pharmacology , agonist , muscimol , mitochondrion , receptor , neurodegeneration , ischemia , chemistry , medicine , endocrinology , biology , apoptosis , programmed cell death , biochemistry , disease
Gamma‐aminobutyric acid is the inhibitory neurotransmitter and has been identified in mitochondria. Because the release of mitochondrial factors is known to correlate with acute neurological damage, we proposed to investigate the possible neuroprotective effects of GABA‐A receptors in cerebral ischemia. In this study transient ischemia was induced in mice by occlusion in the middle of the carotid artery (MACO). Effects of GABA‐A receptor agonist (muscimol) were first studied in oxygen/glucose deprivation‐induced death of neuronal cells. Mitochondrial membrane potential, cytochrome‐c release, caspase 3 activation, the infarct volume and neurological function were examined in the absence or presence of muscimol. Our results shows that GABA‐A receptor agonist inhibits oxygen/glucose deprivation‐induced cell death, loss of mitochondrial membrane potential, downstream release of cytochrome‐C, which activates the caspase apoptotic signaling cascade. Furthermore, it decreases infarct size and improves neurological scores after MACO in mice. This study indicated that GABA‐A receptor is neuroprotective against cerebral ischemia. It also suggested mitochondrial permeability transition might be a valuable therapeutic target for acute neurodegeneration. Supported by NIH grant # HL‐71010 & NS‐51568 to SCT.