缺氧新生儿大脑中突触发育受阻。
Disrupted synaptic development in the hypoxic newborn brain.
作者信息
Curristin Sheila M, Cao Anjun, Stewart William B, Zhang Heping, Madri Joseph A, Morrow Jon S, Ment Laura R
机构信息
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15729-34. doi: 10.1073/pnas.232568799. Epub 2002 Nov 15.
Abstract
Infants born prematurely risk significant life-long cognitive disability, representing a major pediatric health crisis. The neuropathology of this cohort is accurately modeled in mice subjected to sublethal postnatal hypoxia. Massively parallel transcriptome analysis using cDNA microchips (9,262 genes), combined with immunohistochemical and protein assays, reveals that sublethal hypoxia accentuates genes subserving presynaptic function, and it suppresses genes involved with synaptic maturation, postsynaptic function, and neurotransmission. Other significantly affected pathways include those involved with glial maturation, vasculogenesis, and components of the cortical and microtubular cytoskeleton. These patterns reveal a global dysynchrony in the maturation programs of the hypoxic developing brain, and offer insights into the vulnerabilities of processes that guide early postnatal cerebral maturation.
摘要
早产婴儿面临严重的终身认知残疾风险，这是一个重大的儿科健康危机。在经历亚致死性出生后缺氧的小鼠中可以准确模拟这一群体的神经病理学。使用cDNA微芯片（9262个基因）进行的大规模平行转录组分析，结合免疫组织化学和蛋白质检测，发现亚致死性缺氧会加剧维持突触前功能的基因表达，同时抑制与突触成熟、突触后功能和神经传递相关的基因。其他受到显著影响的途径包括与神经胶质成熟、血管生成以及皮质和微管细胞骨架成分相关的途径。这些模式揭示了缺氧发育中大脑成熟程序的整体失调，并为指导出生后早期脑成熟的过程中的脆弱性提供了见解。
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