Sex-specific effect of prenatal alcohol exposure on N-methyl-D-aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice.
Sex-specific effect of prenatal alcohol exposure on N-methyl-D-aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice.
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DOI：
10.1111/acer.14697
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Brigman JL
中科院分区：
文献类型：
--
作者：
Licheri V;Chandrasekaran J;Bird CW;Valenzuela CF;Brigman JL
怀孕期间饮酒会产生持续到成年的行为和认知缺陷，包括执行功能，学习，规划和认知灵活性的损害。我们之前已经表明，适度的产前酒精暴露（PAE）显着损害逆转学习，一种由不同的大脑区域，包括眶额叶皮层（OFC）介导的跨物种的灵活性的措施。同样，含有GluN 2B亚基的N-甲基-D-天冬氨酸受体（NMDAR）的遗传或药理学失活也会损害记忆学习。在目前的研究中，我们测试的假设，中度PAE持续改变的数量和功能的GluN 2B亚基含有NMDARs在OFC锥体神经元的成年小鼠。我们使用FASD的啮齿动物模型，并让后代不受干扰直到成年。使用全细胞膜片钳记录，我们评估了90-100天大的雄性和雌性PAE和对照小鼠切片中的NMDAR功能。在不存在和存在GluN 2B拮抗剂Ro 25 -6981（1 μM）的情况下，记录药理学分离的NMDA受体介导的诱发兴奋性突触后电流（NMDA-eEPSC）。在同窝仔的一个子集中，使用蛋白质印迹技术评价突触部分中GluN 2B蛋白表达的水平。我们的研究结果表明，PAE雌性小鼠的NMDA-eEPSC振幅显著大于对照组（约23%），而PAE诱导了来自雄性小鼠切片中记录的锥体神经元NMDA-eEPSC电流密度的显著降低（约17%）。NMDA eEPSC衰变时间在两种性别的PAE暴露小鼠中均未受到影响。含有GluN 2B亚基的NMDAR对eEPSC的贡献没有被PAE显著改变。此外，在PAE雄性和雌性的突触部分中蛋白质表达没有显著变化。这些结果表明，低至中度PAE调制NMDAR功能在锥体神经元的性别特异性的方式，虽然我们没有发现证据表明，这是由功能障碍的突触GluN 2B亚基含有NMDAR。
Alcohol consumption during pregnancy can produce behavioral and cognitive deficits that persist into adulthood including impairments in executive functions, learning, planning and cognitive flexibility. We have previously shown that moderate prenatal alcohol exposure (PAE) significantly impairs reversal learning, a measure of flexibility mediated across species by different brain areas including the orbital frontal cortex (OFC). Reversal learning is likewise impaired by genetic or pharmacological inactivation of GluN2B subunit-containing N-Methyl-D-aspartate receptors (NMDARs). In the current study, we tested the hypothesis that moderate PAE persistently alters the number and function of GluN2B subunit-containing NMDARs in OFC pyramidal neurons of adult mice. We used a rodent model of FASD and left offspring undisturbed until adulthood. Using whole-cell patch-clamp recordings we assessed NMDAR function in slices from 90–100-day-old male and female PAE, and control mice. Pharmacologically-isolated NMDA receptor-mediated evoked excitatory post-synaptic currents (NMDA-eEPSCs) were recorded in the absence and presence of the GluN2B antagonist, Ro25–6981(1 μM). In a subset of littermates, the level of GluN2B protein expression in the synaptic fraction was evaluated using western blotting technique. Our results indicate that PAE females show significantly larger (~23%) NMDA-eEPSC amplitude than controls, while PAE induced a significant decrease (~ 17%) in NMDA-eEPSC current density of pyramidal neurons recorded in slices coming from male mice. NMDA eEPSC decay time was not affected in PAE-exposed mice from either sex. The contribution of GluN2B subunit-containing NMDARs to the eEPSCs was not significantly altered by PAE. Moreover, there were no significant changes in protein expression in the synaptic fraction of PAE males and females. These findings suggest that low-to-moderate PAE modulates NMDAR function in pyramidal neurons in a sex specific manner, although we did not find evidence that this is mediated by dysfunction of synaptic GluN2B subunit-containing NMDARs.
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DOI：
10.1097/01.alc.0000156125.50577.ec
发表时间：
2005-03-01
影响因子：
3.2
作者：
Burden, MJ;Jacobson, SW;Jacobson, JL
通讯作者：
Jacobson, JL
影响因子：
4.7
作者：
Marquardt, Kristin;Cavanagh, James F.;Brigman, Jonathan L.
通讯作者：
Brigman, Jonathan L.
影响因子：
2.9
作者：
Lynch, Mary Ellen;Kable, Julie A.;Coles, Claire D.
通讯作者：
Coles, Claire D.
影响因子：
3.7
作者：
Bird CW;Candelaria-Cook FT;Magcalas CM;Davies S;Valenzuela CF;Savage DD;Hamilton DA
通讯作者：
Hamilton DA
影响因子：
3.3
作者：
Goebel-Goody, S. M.;Davies, K. D.;Browning, M. D.
通讯作者：
Browning, M. D.