CHRONIC FLUOXETINE TREATMENT INDUCES STRUCTURAL PLASTICITY AND SELECTIVE CHANGES IN GLUTAMATE RECEPTOR SUBUNITS IN THE RAT CEREBRAL CORTEX
CHRONIC FLUOXETINE TREATMENT INDUCES STRUCTURAL PLASTICITY AND SELECTIVE CHANGES IN GLUTAMATE RECEPTOR SUBUNITS IN THE RAT CEREBRAL CORTEX
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DOI：
10.1016/j.neuroscience.2010.04.035
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发表时间：
2010-08-11
期刊：
影响因子：
3.3
通讯作者：
Wyneken, U.
中科院分区：
文献类型：
--
作者：
Ampuero, E.;Rubio, F. J.;Wyneken, U.
据推测，长期服用抗抑郁药物会诱导多巴胺能前脑突触的结构和分子适应延迟，这可能是情绪改善的基础。为了进一步了解大脑皮层的这些变化，用氟西汀（flx）治疗大鼠4周。这些动物表现出减少焦虑和习得性无助。采用免疫印迹和免疫组织化学方法分析前脑N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体亚单位（NR 1、NR 2A、NR 2B、GluR 1和GluR 2）水平。这两种方法都证实了NR 2A、GluR 1和GluR 2的上调，这在压后颗粒B皮质（RSG B）中尤其显著。然而，当分析突触后密度和突触膜中的亚基含量时，我们发现NR 2A和GluR 2增加，而不是GluR 1。相反，GluR 1在含有细胞内膜的微粒体部分中增加。NR 1和GluR 2从突触后致密物和突触膜共免疫沉淀。在免疫沉淀物中，NR 2A增加，而GluR 1减少，支持受体化学计量的变化。亚基水平的变化与树突棘密度和大的，蘑菇型棘的上调。这些分子和结构上的适应可能与长期固定处理后神经网络的稳定有关。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
It has been postulated that chronic administration of antidepressant drugs induces delayed structural and molecular adaptations at glutamatergic forebrain synapses that might underlie mood improvement. To gain further insight into these changes in the cerebral cortex, rats were treated with fluoxetine (flx) for 4 weeks. These animals showed decreased anxiety and learned helplessness. N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit levels (NR1, NR2A, NR2B, GluR1 and GluR2) were analysed in the forebrain by both western blot of homogenates and immunohistochemistry. Both methods demonstrated an upregulation of NR2A, GluR1 and GluR2 that was especially significant in the retrosplenial granular b cortex (RSGb). However, when analysing subunit content in postsynaptic densities and synaptic membranes, we found increases of NR2A and GluR2 but not GluR1. Instead, GluR1 was augmented in a microsomal fraction containing intracellular membranes. NR1 and GluR2 were co-immunoprecipitated from postsynaptic densities and synaptic membranes. In the immunoprecipitates, NR2A was increased while GluR1 was decreased supporting a change in receptor stoichiometry. The changes of subunit levels were associated with an upregulation of dendritic spine density and of large, mushroom-type spines. These molecular and structural adaptations might be involved in neuronal network stabilization following long-term fix treatment. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.