Neuroplastin65敲除通过调控中枢5-HT影响小鼠的焦虑样行为

发布时间：2018-05-03 08:44

  本文选题：neuroplastin + neuroplastin　； 参考：《神经解剖学杂志》2017年06期

【摘要】：目的:研究neuroplastin65(NP65)敲除对小鼠焦虑样行为的影响并初步探讨其机制。方法:成年NP65敲除(NP65~(-/-))小鼠和同基因型背景的野生型(wild type,WT)小鼠,通过Western Blot鉴定NP65~(-/-)小鼠;用旷场实验、探洞实验和埋珠实验检测小鼠的焦虑水平;ELISA检测小鼠海马、前额叶皮质和纹状体谷氨酸和5-羟色胺(5-hydroxytryptamine,5-HT)的含量;5-HT合成酶色氨酸羟化酶2(tryptophan hydroxylase 2,TPH2)免疫荧光染色观察小鼠脑干中缝核5-HT能神经元;Western Blot检测小鼠脑干TPH2的蛋白表达。结果:与WT小鼠相比,在旷场实验中,NP65~(-/-)小鼠进入中心区的次数显著减少(P0.001),中心区停留时间显著降低(P0.001),运动总距离和平均运动速度无显著变化。探洞实验中,NP65~(-/-)小鼠探洞次数显著增加(P0.001)、探洞时间增多(P0.05)、后肢竖立次数减少(P0.01)和排便次数增多(P0.001)。埋珠实验中,NP65~(-/-)小鼠掩埋潜伏期延长(P0.05),埋珠个数显著减少(P0.05)。神经递质检测结果显示:NP65~(-/-)小鼠海马、前额叶皮质和纹状体谷氨酸的含量不变,海马5-HT的含量显著减少(P0.05),但前额叶皮质和纹状体5-HT的含量没有显著性差异。免疫荧光染色观察到NP65~(-/-)小鼠脑干中缝核TPH2阳性细胞数目显著减少(P0.05)。Western Blot分析显示:NP65~(-/-)小鼠脑干TPH2的蛋白表达量显著降低(P0.05)。结论:NP65敲除导致小鼠表现出显著的焦虑样行为,可能与脑干中缝核TPH2表达减少而导致海马5-HT含量降低有关。
[Abstract]:Aim: to study the effect of neuroplastin 65 (NP65) knockout on anxiety like behavior in mice and its mechanism. Methods: adult NP65 knockout (NP65) and wild type (WTW) mice were identified by Western Blot, and the anxiety level of the mice was detected by open field test, burying test and burying test. The level of anxiety was detected by Elisa. The content of glutamate and 5-hydroxytryptamine (5-HT) in prefrontal cortex and striatum; Immunofluorescence staining of 5-HT synthetase tryptophan hydroxylase 2(tryptophan hydroxylase _ 2 (TPH _ 2) was used to detect the protein expression of TPH2 in mouse brain stem by Western Blot. Results: compared with WT mice, in the open field experiment, the times of entering the central area were significantly decreased, the residence time of the central area was significantly decreased, and the total distance and the average exercise speed were not significantly changed. In the hole exploration experiment, the number of holes in NP65 / -) mice increased significantly (P 0.001), the time of hole probing increased (P 0.05), the number of erections of hind limbs decreased (P 0.01) and the times of defecation increased (P 0.001). In the bead burying experiment, the burying latency of NP65 / r -) mice was prolonged (P0.05), and the number of buried bead decreased significantly (P0.05). The results of neurotransmitters test showed that the content of glutamate in prefrontal cortex and striatum was unchanged in the hippocampus, and the content of 5-HT in hippocampus decreased significantly (P 0.05), but there was no significant difference in 5-HT content between prefrontal cortex and striatum. Immunofluorescence staining showed that the number of TPH2 positive cells in the nucleus raphe nucleus of the NP65 mice was significantly decreased. Western Blot analysis showed that the protein expression of TPH2 in brain stem of the mice was significantly decreased. Conclusion knockout of brain stem NP65 induces significant anxiety like behavior in mice, which may be related to the decrease of TPH2 expression in the raphe nucleus of brain stem and the decrease of 5-HT content in hippocampus.
【作者单位】： 同济大学医学院解剖组胚与神经生物学系;
【基金】：国家自然科学基金(81371213)
【分类号】：R749.72
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本文编号：1837822