期刊
NEUROSCIENCE LETTERS
卷 328, 期 1, 页码 33-36出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0304-3940(02)00448-2
关键词
apoptosis; excitotoxicity; neurons; allopregnanolone; progesterone; neurosteroids; NT2 neurons
Progesterone modulates gamma-aminobutyric acid and excitatory amino acid neurotransmitter systems and has neuroprotective properties in models of hypoxia-ischemia. This study examined the in vitro effects of allopregnanolone, the active progesterone metabolite, in models of N-methyl-D-aspartate (NMDA)-induced necrosis and apoptosis. Cultured NT2 neurons were exposed to 1 mM NMDA. Lactate dehydrogenase (LDH) release was measured 24 h later. NMDA at a concentration of 1 mM produced a 39 +/- 19% release of total LDH. Exposure to 10 muM allopregnanolone prior to NMDA exposure reduced LDH release by 51% (P = 0.0028). NMDA stimulated apoptotic cell changes defined by terminal dUTP nick-end labeling (TUNEL) and 5,5',6,6- tetrachloro-1,1,3,3'-tetra ethlybenzimidazolycarbocyanide iodide staining were reduced to baseline values by both 10 muM allopregnanolone and 100 muM MK-801. Pretreatment with allopregnanolone (0-10 muM) reduced the percentage of TUNEL-positive cells in a dose-dependent manner (EC50 = 2.7 +/- 0.1 nM). Physiologic concentrations of allopregnanolone provided protection against both necrotic and apoptotic injury induced by NMDA excitotoxicity. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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