Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity.
Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity.
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DOI：
10.1016/j.pbb.2011.10.013
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Barron S
中科院分区：
文献类型：
--
作者：
Lewis B;Wellmann KA;Kehrberg AM;Carter ML;Baldwin T;Cohen M;Barron S
NMDAR介导的兴奋性毒性与胎儿乙醇暴露后的一些损伤有关。先前的研究表明，神经元细胞死亡和一些行为缺陷可以通过戒断期间的NMDAR拮抗作用来减少，包括拮抗含有NR 2B亚基的受体亚群。为了进一步研究NR 2B参与，我们选择了一种化合物CP-101，606（CP），其选择性地结合NR 2B/2B化学计量，用于体外和体内分析。对于体外研究，将海马外植体暴露于乙醇10天，然后在去除乙醇后24小时，通过碘化丙啶荧光定量细胞损伤。CP（10和25 nM）可预防体外乙醇戒断相关的神经毒性。在PND 1-7给予体内乙醇暴露，并在停止后21小时给予CP。活动（PND 20 -21）、运动技能（PND 31 -33）和迷宫导航（PND 43 -44）均易受乙醇损伤影响; CP（15 mg/kg）治疗可挽救这些缺陷。我们的研究结果表明，CP-101，606，一种阻断NR 2B/2B受体的药物，可以减少我们的啮齿动物模型中“孕晚期”酒精暴露的一些损害作用。进一步的工作显然是必要的神经保护潜力，这种药物在发育中的大脑。
NMDAR-mediated excitotoxicity has been implicated in some of the impairments following fetal ethanol exposure. Previous studies suggest that both neuronal cell death and some of the behavioral deficits can be reduced by NMDAR antagonism during withdrawal, including antagonism of a subpopulation of receptors containing NR2B subunits. To further investigate NR2B involvement, we selected a compound, CP-101,606 (CP) which binds selectively to NR2B/2B stoichiometries, for both in vitro and in vivo analyses. For the in vitro study, hippocampal explants were exposed to ethanol for 10 days and then 24 h following removal of ethanol, cellular damage was quantified via propidium iodide fluorescence. In vitro ethanol withdrawal-associated neurotoxicity was prevented by CP (10 and 25 nM). In vivo ethanol exposure was administered on PNDs 1–7 with CP administered 21 h following cessation. Activity (PND20–21), motor skills (PND31–33), and maze navigation (PND43–44) were all susceptible to ethanol insult; treatment with CP (15 mg/kg) rescued these deficits. Our findings show that CP-101,606, a drug that blocks the NR2B/2B receptor, can reduce some of the damaging effects of “3rd trimester” alcohol exposure in our rodent model. Further work is clearly warranted on the neuroprotective potential of this drug in the developing brain.
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影响因子：
2.9
作者：
DAVIDSON, M;SHANLEY, B;WILCE, P
通讯作者：
WILCE, P
影响因子：
2.9
作者：
BLANCHARD, BA;RILEY, EP;HANNIGAN, JH
通讯作者：
HANNIGAN, JH
DOI：
10.1097/00000374-200003000-00007
发表时间：
2000-03-01
影响因子：
3.2
作者：
Girard, TA;Xing, HC;Wainwright, PE
通讯作者：
Wainwright, PE
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J
影响因子：
2.7
作者：
GOODLETT, CR;PETERSON, SD
通讯作者：
PETERSON, SD