Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus.
Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus.
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DOI：
10.1016/j.neuroscience.2011.04.069
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发表时间：
2011-08-11
期刊：
影响因子：
3.3
通讯作者：
Gondre-Lewis, M. C.
中科院分区：
文献类型：
--
作者：
Wang, H.;Davila-Garcia, M. I.;Yarl, W.;Gondre-Lewis, M. C.
尼古丁过早激活烟碱乙酰胆碱受体（nAChR）会对学习和行为产生短期和长期影响。在这项研究中，目的是确定产前尼古丁暴露如何影响产后发育过程中海马谷氨酸信号的组成部分。我们研究了在子宫内暂时限制接触盐水或尼古丁 14 天后，从出生后第 1 天 (P) 到第 63 天，nAChR 和谷氨酸受体对 α-氨基-3-羟基-5-甲基异恶唑-4-丙酸 (AMPA) 和 N-甲基-D-天冬氨酸 (NMDA) 的调节。我们分析了与 AMPAR 和 NMDAR 信号传导相关的突触后密度成分：钙/钙调蛋白依赖性蛋白激酶 II α (CaMKIIα)、钙调蛋白 (CaM) 和突触后密度 95 (PSD95)，以及突触前定位的突触体相关蛋白 25 (SNAP25)。在 P1 时，AMPAR 亚基 GluR1 的表达显着升高，但 GluR2 没有；NMDAR 亚基 NR1、NR2a 和 NR2d 的表达显着升高，但 NR2b 没有显着升高。 NR2c 未检测到。在 P1，突触后蛋白 CaMKIIα、CaM 和 PSD95 以及突触前 SNAP25 也显着上调。谷氨酸受体和信号蛋白表达的增强与产前暴露于尼古丁的海马中[3H] Epibatidine (EB)结合水平的升高相伴随，表明α4β2 nAChR可能影响P1时海马的谷氨酸能功能。到 P14，[3H]EB 结合和亚基 GluR1、GluR2、NR1、NR2a、NR2b、NR2c 或 NR2d 的表达水平似乎都没有因产前尼古丁而改变。然而，尼古丁治疗后 CaMKIIα 显着上调，而 CaM 在 P14 时表现出下调。尼古丁的影响在 P63 的年轻人大脑中持续存在。他们在海马匀浆中表现出显着下调的 GluR2、NR1 和 NR2c 表达水平，并且在 CA1、CA2、CA3 和齿状回区域中 [3H]AMPA 结合的整体分布显着减弱。我们的结果表明，产前接触尼古丁可以通过增强或抑制 AMPAR 和 NMDAR 或其信号成分的可用性来调节整个产后发育的谷氨酸信号系统。在成人中，NMDAR 组装所需的 NR1 亚基和对 AMPAR 的组装、运输和生物物理特性很重要的 GluR2 的持续抑制表明，在产前限制接触后，尼古丁可能会改变成人的离子型谷氨酸受体化学计量和功能特性。
Untimely activation of nicotinic acetylcholine receptor (nAChR) by nicotine results in short- and long-term consequences on learning and behavior. In this study, the aim was to determine how prenatal nicotine exposure affects components of glutamatergic signaling in the hippocampus during postnatal development. We investigated regulation of both nAChRs and glutamate receptors for α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA), from postnatal day (P) 1 to P63 after a temporally restricted exposure to saline or nicotine for 14 days in utero. We analyzed postsynaptic density components associated with AMPAR and NMDAR signaling: Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), Calmodulin (CaM), and postsynaptic density-95 (PSD95), as well as presynaptically localized synaptosomal-associated protein 25 (SNAP25). At P1, there was significantly heightened expression of AMPAR subunit GluR1 but not GluR2, and of NMDAR subunits NR1, NR2a and NR2d but not NR2b. NR2c was not detectable. At P1, the postsynaptic proteins CaMKIIα, CaM, and PSD95 were also significantly upregulated, together with presynaptic SNAP25. This enhanced expression of glutamate receptors and signaling proteins was concomitant with elevated levels of [3H] Epibatidine (EB) binding in prenatal nicotine-exposed hippocampus, indicating that α4β2 nAChR may influence glutamatergic function in the hippocampus at P1. By P14, neither [3H]EB binding nor the expression levels of subunits GluR1, GluR2, NR1, NR2a, NR2b, NR2c, or NR2d seemed changed with prenatal nicotine. However, CaMKIIα was significantly upregulated with nicotine treatment while CaM showed downregulation at P14. The effects of nicotine persisted in young adult brains at P63. They exhibited significantly downregulated GluR2, NR1, and NR2c expression levels in hippocampal homogenates and a considerably muted overall distribution of [3H]AMPA binding in areas CA1, CA2, CA3, and the dentate gyrus. Our results suggest that prenatal nicotine exposure can regulate the glutamatergic signaling system throughout postnatal development by enhancing or inhibiting availability of AMPAR and NMDAR or their signaling components. The persistent depression, in adults, of the requisite NR1 subunit for NMDAR assembly, and of GluR2, important for assembly, trafficking, and biophysical properties of AMPAR, indicates that nicotine may alter ionotropic glutamate receptor stoichiometry and functional properties in adults after prenatally restricted exposure.
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影响因子：
10.4
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/s0169-328x(01)00230-3
发表时间：
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期刊：
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作者：
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作者：
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