γ-氨基丁酸A型（GABAA）受体激动剂四氢嘧啶在器官型海马脑片培养物中具有神经保护作用。

The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures.

作者信息

Kristensen Bjarne W, Noraberg Jens, Zimmer Jens

机构信息

Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winsløwparken 21, DK-5000 Odense C, Denmark.

出版信息

Brain Res. 2003 May 30;973(2):303-6. doi: 10.1016/s0006-8993(03)02550-2.

DOI:10.1016/s0006-8993(03)02550-2

PMID:12738075

Abstract

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.

摘要

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。