Kristensen Bjarne W, Noraberg Jens, Zimmer Jens
Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winsløwparken 21, DK-5000 Odense C, Denmark.
Brain Res. 2003 May 30;973(2):303-6. doi: 10.1016/s0006-8993(03)02550-2.
The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneurons, were examined in hippocampal slice cultures exposed to N-methyl-D-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100-1000 microM) was neuroprotective in slice cultures co-exposed to NMDA (10 microM) for 48 h, while muscimol (100-1000 microM) and ATPA (1-3 microM) were without effect. The results demonstrate that direct GABA(A) agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo.
在暴露于N-甲基-D-天冬氨酸（NMDA）的海马切片培养物中，研究了GABA(A)受体激动剂THIP（4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇）和蝇蕈醇以及选择性GluR5红藻氨酸受体激动剂ATPA（(RS)-2-氨基-3-(3-羟基-5-叔丁基异恶唑-4-基)丙酸）的潜在神经保护作用，后者可激活GABA能中间神经元。通过对碘化丙啶（PI）摄取的光密度测量来量化NMDA诱导的兴奋性毒性。THIP（100 - 1000微摩尔）对共同暴露于NMDA（10微摩尔）48小时的切片培养物具有神经保护作用，而蝇蕈醇（100 - 1000微摩尔）和ATPA（1 - 3微摩尔）则无作用。结果表明，如先前在体内所提示的，直接的GABA(A)激动作用可在体外介导海马体中的神经保护作用。
