Abstract

Our previous study showed that datumetine modulates NMDAR activity with long term exposure leading to memory deficit and altered NMDAR signaling. We aim to explore the neurotransmitters perturbations of acute datumetine-NMDAR interaction. Fifteen C57/BL6 mice were used for the study, they are divided into three groups of 5 animals each. Animals were administered DMSO (DMSO/Control), 0.25 mg/kg body weight of datumetine (0.25 Datumetine) and 1 mg/kg bodyweight of datumetine (1.0 Datumetine) intraperitoneally for 14 days. At the end of treatment, animals were euthanized in isofluorane chamber, perfused transcardially with 1XPBS followed by PFA. Immunofluorescence procedure was done to check the distribution of neurons, astrocytes, microglia and major neuronal subtypes in the hippocampus. Expansion and electron microscopy techniques were used to assess the condition of the synapses. Quantitative data were expressed as mean ± SEM and analyzed using ANOVA with Tukey post hoc using p < 0.05 as significant. Datumetine increased the expression of CD11b, GFAP, vGlut1, GABA, CHRNA7 and TH while expression of TrPH and NeuN were reduced in the hippocampus compared to control animals. Synaptic loss was evident in datumetine exposed animals with reduced synaptic vesicles accompanied by a thickness of postsynaptic density than that of control animals. This study concludes that acute datumetine exposure alters hippocampal neurotransmitter systems.

摘要

我们之前的研究表明，达美汀调节 NMDAR 活性，长期暴露会导致记忆缺陷和 NMDAR 信号改变。我们旨在探索急性达美汀-NMDAR 相互作用的神经递质扰动。15 只 C57/BL6 小鼠用于研究，它们被分成三组，每组 5 只动物。腹膜内给予动物 DMSO (DMSO/对照)、0.25 mg/kg 体重的达美汀 (0.25 Datumetine) 和 1 mg/kg 体重的达美汀 (1.0 Datumetine) 14 天。在治疗结束时，动物在异氟烷室中被安乐死，经心灌注 1XPBS，然后灌注 PFA。进行免疫荧光检查以检查海马中神经元、星形胶质细胞、小胶质细胞和主要神经元亚型的分布。扩展和电子显微镜技术用于评估突触的状况。定量数据表示为平均值±SEM，并使用 ANOVA 和 Tukey post hoc 使用p  < 0.05 为显着。与对照动物相比，达美汀增加了海马中 CD11b、GFAP、vGlut1、GABA、CHRNA7 和 TH 的表达，而 TrPH 和 NeuN 的表达降低。与对照动物相比，使用达美汀的动物突触损失明显，突触小泡减少，突触后密度增加。本研究得出结论，急性达美汀暴露会改变海马神经递质系统。