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少突胶质细胞在出生后早期发育过程中作为神经元网络的调节者。

Oligodendrocytes as regulators of neuronal networks during early postnatal development.

机构信息

Department of Microbiology and Molecular Genetics and U904 INSERM/UCI, University of California Irvine, Irvine, California, United States of America.

出版信息

PLoS One. 2011 May 12;6(5):e19849. doi: 10.1371/journal.pone.0019849.

Abstract

Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development.

摘要

少突胶质细胞是负责形成髓鞘的神经胶质细胞。髓鞘形成发生在出生后的第一周内,在啮齿类动物中,出生后第三周完成。髓鞘确保神经冲动的快速传导;在成年后,髓鞘蛋白对损伤后轴突的生长和再生具有抑制作用。在大脑发育过程中,起源于前-后轴上多个位置的少突胶质细胞前体细胞积极增殖并迁移,以殖民整个大脑。少突胶质细胞和神经元之间的初始相互作用是否在髓鞘形成之前就具有功能作用,目前仍不完全清楚。在本文中,我们通过在小脑发育过程中转基因靶向清除增殖性少突胶质细胞来解决这个问题。有趣的是,我们发现,在出生后第 1 天(P1)清除少突胶质细胞会严重影响小脑回路的建立。我们观察到参与轴突生长、导向和突触可塑性的分子表达出现显著失调。这些影响伴随着在消融方案开始后 4 小时观察到的神经丝染色的显著增加,这可能依赖于小脑纤维的发芽。少突胶质细胞消融改变了 Purkinje 神经元中离子型谷氨酸受体的定位和功能。这些结果显示了一种新的少突胶质细胞功能,它在早期出生后大脑发育过程中表达,这些细胞参与了小脑回路的形成,并影响其发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/3093406/68734ec64989/pone.0019849.g001.jpg

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