FIRST AND SECOND GENERATION ANTIPSYCHOTICS DIFFERENTIALLY AFFECT STRUCTURAL AND FUNCTIONAL PROPERTIES OF RAT HIPPOCAMPAL NEURON SYNAPSES
FIRST AND SECOND GENERATION ANTIPSYCHOTICS DIFFERENTIALLY AFFECT STRUCTURAL AND FUNCTIONAL PROPERTIES OF RAT HIPPOCAMPAL NEURON SYNAPSES
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DOI：
10.1016/j.neuroscience.2016.08.055
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发表时间：
2016-11-19
期刊：
影响因子：
3.3
通讯作者：
Faissner, Andreas
中科院分区：
文献类型：
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作者：
Gottschling, Christine;Geissler, Maren;Faissner, Andreas
患有精神障碍精神分裂症的患者的治疗需要使用抗精神病药物，其被分为两个不同的组，第一代（FGA）和第二代抗精神病药物（SGA）。本研究比较了氟哌啶醇和氟哌噻吨两种FGA与SGA奥氮平对胚胎大鼠海马神经元突触形成和突触活动的影响。为此，使用神经元和星形胶质细胞在完全限定培养基中的间接共培养系统研究了神经元束膜网（PNNs）的发育、突触的形成以及在控制和治疗条件下产生的自发网络活动。由突触周围的细胞外基质超结构组成的PNN的数量和范围在海马神经元中没有被抗精神病药物改变。相反，用氟哌啶醇处理海马神经元导致轻微减少，而奥氮平诱导13天后结构性突触数量显着增加。这种差异的影响，突触数量也反映在神经元网络的自发活动，监测多电极阵列（MEA）。在这种情况下，应用氟哌啶醇减少，而奥氮平显着增强网络活动。出乎意料的是，被认为是FGA的氟哌噻吨引起了与SGA奥氮平相似的作用，因为它增加了突触数量以及网络活动。我们的初步研究提供了一个概念证明，神经元-星形胶质细胞共培养模型可用于研究抗精神病药物对神经元细胞生物学关键参数的影响。从而为抗精神病药物治疗精神分裂症的比较分析提供依据。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The therapy of patients suffering the psychiatric disorder schizophrenia requires the usage of antipsychotic drugs that are classified into two different groups, the first-generation (FGAs) and the second-generation antipsychotics (SGAs). This study compares the effects of the two FGAs haloperidol and flupentixol with those of the SGA olanzapine on synapse formation and synaptic activity of embryonic rat hippocampal neurons. To this end, the development of perineuronal nets (PNNs), the formation of synapses and the resulting spontaneous network activity under control and treatment conditions were studied using an indirect co-culture system of neurons and astrocytes in completely defined media. The number and extent of PNNs that consist of extracellular matrix superstructures surrounding synapses was not altered in hippocampal neurons by exposure to antipsychotic drugs. In contrast treatment of hippocampal neurons with haloperidol led to a slight decrease whereas olanzapine induced a significant increase of the number of structural synapses after 13 days. This differential effect concerning synapse numbers was also reflected in the spontaneous activity of neuronal networks, as monitored on multielectrode arrays (MEAs). In that context, application of haloperidol reduced while olanzapine significantly enhanced network activity. Unexpectedly, flupentixol that is regarded as an FGA caused similar effects than the SGA olanzapine in that it augmented synapse number as well as network activity. Our pilot study provides a proof of concept that the neuron-astrocyte co-culture model can be used to investigate the impact of antipsychotics on pivotal parameters of neuronal cell biology. Thereby, it may support the comparative analysis of antipsychotics applied in the therapy of schizophrenia. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.