Moderate prenatal alcohol exposure enhances GluN2B containing NMDA receptor binding and ifenprodil sensitivity in rat agranular insular cortex.
Moderate prenatal alcohol exposure enhances GluN2B containing NMDA receptor binding and ifenprodil sensitivity in rat agranular insular cortex.
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DOI：
10.1371/journal.pone.0118721
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hamilton DA
中科院分区：
文献类型：
--
作者：
Bird CW;Candelaria-Cook FT;Magcalas CM;Davies S;Valenzuela CF;Savage DD;Hamilton DA
孕期酒精暴露影响不同脑区谷氨酸能神经递质受体的表达和功能。这项研究是为了填补目前关于酒精相关的额叶皮质谷氨酸能受体改变的区域特异性的知识空白。我们通过放射配基结合的方法，对孕期暴露于中等水平酒精的成年大鼠的无颗粒岛叶皮质(AID)、外侧眼眶区(LO)、前皮质(PRL)和初级运动皮质(M1)的谷氨酸能神经递质受体(AMPAR、NMDARs、含GluN2B的NMDARs、mGluR1s和mGluR5s)的亚区表达和功能进行了量化。在酒精暴露的大鼠AID中，观察到含有GluN2B的NMDARs的表达增加，而在其他区域的表达略有减少。随后，我们在全细胞膜片钳制备中进行了薄片电生理测量，以定量AID层II/III层锥体神经元中NMDAR介导的兴奋性突触后电流(EPSCs)对GluN2B负变构调节剂依芬普地尔的敏感性。与GluN2B表达增加一致的是，与糖精暴露的对照组动物相比，异丙苯地尔导致产前酒精暴露大鼠NMDAR介导的EPSCs更大程度的减少。未观察到AMPAR介导的EPSCs或AMPAR/NMDARs比值的变化。总之，这些数据表明，适度的产前酒精暴露对AID中包含GluN2B的受体有显著而持久的影响，这可能有助于解释依赖于该区域的与酒精相关的学习和行为变化。
Prenatal exposure to alcohol affects the expression and function of glutamatergic neurotransmitter receptors in diverse brain regions. The present study was undertaken to fill a current gap in knowledge regarding the regional specificity of ethanol-related alterations in glutamatergic receptors in the frontal cortex. We quantified subregional expression and function of glutamatergic neurotransmitter receptors (AMPARs, NMDARs, GluN2B-containing NMDARs, mGluR1s, and mGluR5s) by radioligand binding in the agranular insular cortex (AID), lateral orbital area (LO), prelimbic cortex (PrL) and primary motor cortex (M1) of adult rats exposed to moderate levels of ethanol during prenatal development. Increased expression of GluN2B-containing NMDARs was observed in AID of ethanol-exposed rats compared to modest reductions in other regions. We subsequently performed slice electrophysiology measurements in a whole-cell patch-clamp preparation to quantify the sensitivity of evoked NMDAR-mediated excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of AID to the GluN2B negative allosteric modulator ifenprodil. Consistent with increased GluN2B expression, ifenprodil caused a greater reduction in NMDAR-mediated EPSCs from prenatal alcohol-exposed rats than saccharin-exposed control animals. No alterations in AMPAR-mediated EPSCs or the ratio of AMPARs/NMDARs were observed. Together, these data indicate that moderate prenatal alcohol exposure has a significant and lasting impact on GluN2B-containing receptors in AID, which could help to explain ethanol-related alterations in learning and behaviors that depend on this region.
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影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
影响因子：
4.8
作者：
Costa, ET;Olivera, DS;Valenzuela, CF
通讯作者：
Valenzuela, CF
影响因子：
3.7
作者：
Allan, Andrea M.;Goggin, Samantha L.;Caldwell, Kevin K.
通讯作者：
Caldwell, Kevin K.
DOI：
10.1016/s0165-3806(02)00363-2
发表时间：
2002-05-30
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Bellinger, FP;Davidson, MS;Wilce, PA
通讯作者：
Wilce, PA
影响因子：
5.3
作者：
Akashi, Kaori;Kakizaki, Toshikazu;Sakimura, Kenji
通讯作者：
Sakimura, Kenji