胆固醇缺乏作为自闭症的机制:一种酸模型
Morgan R Peltier1,2, Jennifer Behbodikhah2, Heather A Renna3
1Department of Psychiatry and Behavioral Health, Jersey Shore University Medical Center, Neptune, NJ, USA.
概括
瓦尔酸 (VPA) 改变大脑细胞中的胆固醇代谢,影响自闭症谱系障碍 (ASD) 风险. 在微质和神经细胞中,VPA对胆固醇运输基因表达的影响不一致,对胆固醇排泄有不同的影响.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 发展生物学 发展生物学
背景情况:
- 失调的胆固醇代谢越来越多地与自闭症谱系障碍 (ASD) 有关.
- 产前接触抗药物酸 (VPA) 会增加患有胎儿酸综合征的儿童的ASD发病率.
- 对于VPA对神经元和微质细胞中胆固醇稳态的具体影响尚不清楚.
研究的目的:
- 调查VPA暴露对人类微质细胞 (HMC3) 和神经母细胞瘤 (SH-SY5Y) 细胞系中胆固醇稳态的影响.
- 分析VPA对关键胆固醇载体和代谢酶在mRNA和蛋白质水平表达的影响.
- 在这些细胞模型中评估VPA对胆固醇排放的影响.
主要方法:
- 化HMC3和SH-SY5Y细胞,其中VPA的度不同.
- 对与胆固醇相关的基因 (例如,ABCA1,ABCG1,CD36,27-基酶) 的mRNA和蛋白质表达量的量化.
- 色度测试测量治疗细胞中的胆固醇排放量.
主要成果:
- 在HMC3和SH-SY5Y细胞中,VPA改变了胆固醇载体mRNA和蛋白质水平.
- 在HMC3细胞中,VPA降低了ABCA1mRNA和蛋白质,但增加了ABCG1和CD36mRNA.
- 在SH-SY5Y细胞中,VPA增加了多个胆固醇基因的mRNA,并减少了ABCA1蛋白,同时在高剂量时增加了ABCG1蛋白;胆固醇外流增加在SH-SY5Y细胞中,但不是HMC3细胞.
结论:
- 在微质细胞和神经元细胞中,VPA在转录和转化水平上差异调节胆固醇载体表达.
- 观察到的基因表达的变化并不总是与体外胆固醇排泄能力相关.
- 这些发现强调了VPA对细胞胆固醇代谢的复杂影响,可能导致与ASD相关的神经发育变化.
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