在母体免疫激活后的突触蛋白质组扰乱:识别胚胎和成人海马变化
Anna Y Yotova1, Li-Li Li2, Aet O'Leary3
1Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; Goethe University Frankfurt, Faculty of Biological Sciences, Institute of Cell Biology and Neuroscience, Frankfurt, Germany.
母亲免疫激活 (MIA) 动态改变后代海马蛋白质组. 这些变化影响了突触功能,并与人类的认知和精神病学表型有关,提供了新的研究目标.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 母亲免疫激活 (MIA) 影响后代的神经发育,特别是海马.
- 在MIA诱导的突触变化中的时间和性别差异尚未得到充分理解.
研究的目的:
- 调查MIA后海马体的时间和性别特异性蛋白质变化.
- 确定受MIA影响的突触蛋白及其与人类认知和精神疾病的潜在联系.
主要方法:
- 在小鼠中诱导的MIA使用poly (I:C) 在妊娠第9天.
- 从胚胎和成人后代的海马 synaptoneurosomes的基于质谱的蛋白质组分析.
主要成果:
- 胚胎MIA破坏了脂质,多糖和糖蛋白代谢.
- 成人MIA改变了突触贩运,信号传递,细胞死亡/生长和细胞骨组织.
- 在成年人中,性别特定的多巴胺基和谷氨酸基通路受到影响.
- 50种蛋白质在胚胎和成年阶段都发生了变化,与突触前结构和囊泡功能有关.
- 在50个编码这些蛋白质的基因中,有49个与人类认知/精神病学表型相关.
结论:
- 类似病毒的MIA对正在发育和成熟的海马有动态影响.
- 在产前免疫挑战之后,确定了新的突触点,用于未来的研究.
- 从胚胎到成年阶段改变方向性的蛋白质表明了补偿性适应.
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