The mammalian neocortex is organized into layers distinguished by the size, packing density, and connectivity of their constituent neurons. Many neuropsychiatric illnesses are complex trait disorders with etiologic factors converging on neuronal protein networks. Cortical pathology of neuropsychiatric diseases, such as schizophrenia, is often restricted to, or more pronounced in, certain cortical layers, suggesting that genetic vulnerabilities manifest with laminar specificity. Thus, the ability to investigate cortical layer-specific protein levels in human postmortem brain is highly desirable. Here, we developed and validated a laser capture microdissection-mass spectrometry (LCM-MS) approach to quantify over 200 proteins in cortical layers 3 and 5 of two cohorts of human subjects as well as a monkey model of postmortem interval. LCM-MS was readily implementable and reliably identified protein patterns that differed between cortical layers 3 and 5. Our findings suggest that LCM-MS facilitates the precise quantification of proteins within individual cortical layers from human postmortem brain tissue, providing a powerful tool in the study of neuropsychiatric disease.

中文翻译：

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激光捕获显微切割靶向质谱法：一种对大脑皮层各层内多重蛋白质进行定量的方法。

哺乳动物的新皮质被组织成不同的层，这些层的区别在于其组成神经元的大小、堆积密度和连接性。许多神经精神疾病是复杂的特征性疾病，其病因因素集中在神经元蛋白质网络上。神经精神疾病（例如精神分裂症）的皮质病理学通常局限于某些皮质层，或者在某些皮质层中更为明显，这表明遗传脆弱性表现出层状特异性。因此，非常需要研究人类死后大脑中皮质层特异性蛋白质水平的能力。在这里，我们开发并验证了一种激光捕获显微切割质谱 (LCM-MS) 方法，用于量化两组人类受试者以及死后猴子模型的皮质层 3 和 5 中的 200 多种蛋白质。LCM-MS 易于实施，并且能够可靠地识别皮质层 3 和皮质层 5 之间不同的蛋白质模式。我们的研究结果表明，LCM-MS 有助于对人类死后脑组织的各个皮质层内的蛋白质进行精确定量，为研究提供了强大的工具的神经精神疾病。