The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression
背景
含有NR2B的NMDA（nr2b/NMDA）受体在控制神经发生方面很重要，并参与产生空间记忆。Ro25-6981是这些受体的选择性拮抗剂，并促进神经发生和空间记忆。基因表达调控成年神经发生和神经细胞凋亡的结构间神经解剖特征需要在记忆检索和逆转学习的背景下进行分析。其目的是研究在对nr2b/NMDA受体的阻断后，与基因表达相关的神经遗传过程的空间记忆检索和逆转学习。
方法：
大鼠在Morris水迷宫平台位置训练5天。施用Ro25-6981接着在培训（15-18天或29-32天）测试平台位置（第19天或第33天），然后死后脑组织取样。在海马体、前额皮质和小脑与MWM性能协议的关系中，对三种调节细胞增殖（S100a6）、分化（Ascl1）和细胞凋亡（Casp-3）的基因的表达进行了评估。
结果：在初始的训练后，Ro25-6981在进一步的再训练中增强了视觉空间记忆的恢复能力（第29-32天），但是没有影响视觉空间逆转学习（第33天）。在Ro25-6981治疗后的27天内，小脑S100a6和Casp-3活性分别下降和增加，而海马S100a6和Casp-3表达也相应增加和减少。
结论：总之，Ro25-6981对NR2B/NMDA受体的阻断增强了老鼠的空间记忆检索，但并没有影响视觉空间逆转学习。它还改变了大脑S100a6，Ascl1和Casp-3细胞调控基因表达在所有的概率驱动的神经发生中可能暗示了新的成熟神经元在记忆检索中。
Marina A. Gruden1 & Alexander M. Ratmirov1 & Zinaida I. Storozheva2 & Olga A. Solovieva1 & Vladimir V. Sherstnev1 & Robert D. E. Sewell3Received: 21 February 2018.
Object NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Interstructural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981.
Methods
Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25-6981 was administered (protocol days 6–7) followed by retraining (days 15–18 or 29–32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol.
Result:
Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29–32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment.
Cobclusion:
In summary, Ro25-6981 blockade of NR2B/NMDA receptors enhanced spatial memory retrieval in rats but did not influence visuospatial reversal learning. It also modified brain S100a6, Ascl1, and Casp-3 cell regulator gene expression and in all probability actuated neurogenesis possibly implicating new mature neurons in memory retrieval
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