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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood
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MHC class I molecules are present both pre- and postsynaptically in the visual cortex during postnatal development and in adulthood

机译：MHC I类分子在产后发育期间和成年期均存在于视皮层的突触前和突触后。

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Immune molecules have been discovered recently to play critical roles in the development function, and plasticity of the cerebral cortex. MHC class I (MHCI) molecules are expressed in the central nervous system and regulate activity-dependent refinement of visual projections during late postnatal development They have also been implicated in neurodevelopmental diseases such as schizophrenia and autism. Despite the excitement generated by these unique roles for immune proteins in the brain, little is known about how these molecules regulate cortical connections. The first step toward elucidating the mechanism is to identify the spatial and temporal distribution of MHCI proteins throughout development. Using a pan-specific antibody that recognizes many MHCI variants for biochemistry and immunohistochemistry, we found that MHCI proteins are expressed in the rat visual cortex at all ages examined-during the peak of synaptogenesis, the critical period of synaptic refinement, and adulthood. Their abundance in the cortex peaked during early postnatal development declining during periods of plasticity and adulthood. In contrast to current assumptions, pre-and postem-bedding immunogold electron microscopy (EM) revealed that MHCI proteins were present both pre- and postsynaptically at all ages examined. They were often found in the postsynaptic density and were closely associated with synaptic vesicles in the presynaptic terminal. These results suggest a previously undescribed model in which MHCI molecules function on both sides of the synapse to regulate connectivity in the mammalian visual cortex before, during, and after the establishment of connections.
机译：最近发现免疫分子在大脑皮层的发育功能和可塑性中起关键作用。 MHC I类（MHCI）分子在中枢神经系统中表达，并在产后晚期发育期间调节视投射的活动依赖性细化。它们还与神经发育疾病（例如精神分裂症和自闭症）有关。尽管大脑中免疫蛋白的这些独特作用引起了兴奋，但对于这些分子如何调节皮质连接的了解却很少。阐明该机制的第一步是确定整个发育过程中MHCI蛋白的时空分布。使用能识别许多MHCI变体的泛特异性抗体进行生物化学和免疫组织化学研究，我们发现MHCI蛋白在突触形成的高峰期，突触细化的关键时期和成年期间的所有年龄段的大鼠视皮层中都有表达。它们在皮质中的丰度在出生后早期发育期间达到峰值，在可塑性和成年期下降。与目前的假设相反，床前和床后免疫金电子显微镜（EM）显示MHCI蛋白在所有检查的年龄中均存在于突触前和突触后。它们通常在突触后密度中发现，并且与突触前末端的突触小泡紧密相关。这些结果表明了先前未描述的模型，其中MHCI分子在突触的两侧起作用，以在建立连接之前，之中和之后调节哺乳动物视觉皮层中的连接性。

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