
国际学术期刊《自然》及其系列期刊发表多篇神经科学论文,基于美国PsychAD项目1494名供体的630万例基因表达谱,构建人体前额叶皮层最大规模基因表达图谱,揭示大脑在不同生命阶段的发育转变及其与衰老、认知衰退和阿尔茨海默病等疾病的关联。
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PsychAD项目是由美国国立卫生研究院资助、西奈山伊坎医学院等机构牵头的大型国际研究计划,旨在深入探究阿尔茨海默病及相关神经退行性与神经精神疾病的分子与细胞机制。
中新网北京9月24日电 (记者 孙自法)国际学术期刊《自然》及其系列期刊最新集中发表多篇神经科学论文,以人体前额叶皮层脑区的已知最大规模基因表达图谱,助力探析发育、衰老、退化和疾病。
《自然》及其系列期刊论文分析了来自美国PsychAD项目1494名已故供体大脑的逾630万例基因表达谱。这些研究进一步阐释了前额叶皮层脑区在人生不同阶段的发育,或能用于研究衰老、认知衰退和疾病易感性。
本次系列研究成果相关示意图。施普林格·自然 供图
PsychAD项目合作组介绍,研究发现人类大脑在生命早期和成年晚期会经历极大的发育转变,这些转变会影响认知能力、行为和疾病易感性。分析不同生命阶段的基因表达模式,或能了解大脑如何发生转变,这可用于研究正常衰老以及神经退行性疾病和神经精神疾病的发展。
前额叶皮层脑区参与了关键的认知功能(如解决问题、规划和情绪调节),对年龄相关性退化较敏感,是值得研究的理想脑区,也是PsychAD项目调查阿尔茨海默病等疾病的研究目标。
在PsychAD合作组最新发表的论文中,有三篇在《自然》主刊发表,第一篇论文描述了目前报告的人体背外侧前额叶皮层的最大规模群体尺度单细胞转录组图谱。论文作者评估了年龄段从婴儿期到成年晚期的284名神经典型供体的130万例基因表达谱,用证据表明基因表达如何随时间变化。
这些变化对应了发育早期的大脑重塑,中年时期的稳定(直到约24岁),24岁以后的构成退化,以及65岁以后的细胞重编程。论文作者还鉴定出基因表达变化与早期神经元韧性以及晚年神经元脆弱性的关联。
第二篇论文报道了一个与脑疾病相关的基因表达变化图谱,论文作者评估了PsychAD的完整数据集(来自1494名供体的630万例基因表达谱),其中不仅包含神经典型个体,也包含阿尔茨海默病等脑疾病患者和其他形式的痴呆症、帕金森病、精神分裂症、双相情感障碍个体。
无论研究中的哪种疾病,与基础细胞功能相关的基因表达都有一定相似性。然而,不同形式的痴呆症与帕金森病之间的基因表达变化相似性显著增强,尤其是涉及神经元发育和突触功能的基因。
第三篇论文绘制出脑疾病遗传风险如何影响欧洲裔、非洲裔、美洲裔不同人群的特定细胞类型。论文作者揭示之前未知的数千种基因-性状关联,并发现保守的细胞类型特异性机制。他们认为,该研究结果有助于深入理解神经精神和神经退行性疾病的背后机制。
《自然》同期发表同行专家的“新闻与观点”文章认为,PsychAD项目发表的成果,为理解前额叶皮层内的健康改变以及疾病相关改变提供了研究资源,有望推动发现与神经精神、神经退行性、行为、认知和情感性状相关的基因。
PsychAD合作组另有多篇论文将发表于《自然-医学》《自然-遗传学》《自然-通讯》。
据悉,PsychAD项目是由美国国立卫生研究院资助、西奈山伊坎医学院等机构牵头的大型国际研究计划,旨在深入探究阿尔茨海默病(AD)及相关神经退行性与神经精神疾病的分子与细胞机制。(完)
AI outlook — possibilities, not facts
PsychAD合作组将在《自然-医学》《自然-遗传学》《自然-通讯》发表更多相关论文
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