一个协调的神经元-星细胞计划减少了老化和精神分裂症
Emi Ling1,2, James Nemesh3,4, Melissa Goldman3,4
1Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. eling@broadinstitute.org.
Nature
|March 6, 2024
概括
一个新发现的突触神经元和天体细胞程序 (SNAP) 将大脑细胞的交流与个体差异联系起来. 这项计划
科学领域:
- 神经科学
- 细胞生物学
- 遗传学
背景情况:
- 人类大脑的变化在细胞水平上是不明确的.
- 皮质神经细胞和神经元对大脑功能起着至关重要的作用.
- 精神分裂症和衰老会影响认知灵活性和可塑性.
研究的目的:
- 研究大脑皮层神经元与星球细胞之间的关系.
- 确定个人间差异和神经发育/神经退行性疾病的细胞机制.
- 探索突触神经元和星细胞程序 (SNAP) 在健康和疾病中的作用.
主要方法:
- 来自191名人类捐赠者的前额叶皮质单核RNA测序 (年龄22-97岁).
- 分析包括健康个体和精神分裂症患者.
- 潜在因子分析以确定基因表达关系.
主要成果:
- 在神经元突触基因表达和天体细胞突触/胆固醇合成基因表达之间发现了正相关性,称为突触神经元和天体细胞程序 (SNAP).
- 在精神分裂症患者和老年人中,在星球细胞,谷氨酸性神经元和GABA性神经元中观察到SNAP表达的减少.
- 在SNAP中,基因与精神分裂症相关的遗传风险因素被丰富.
结论:
- SNAP代表了一个关键的细胞机制,
- 在精神分裂症和衰老等疾病中,SNAP的失调可能是病理生理学的趋同点.
- SNAP提供了一个了解认知衰退和大脑可塑性的细胞框架.
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