Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
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DOI：
10.1002/cne.21231
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发表时间：
2007-03-01
影响因子：
2.5
通讯作者：
Fawcett, James W.
中科院分区：
文献类型：
--
作者：
Carulli, Daniela;Rhodes, Kate E.;Fawcett, James W.
细胞外基质分子在出生后发育期间聚集在中枢神经系统神经元周围，形成所谓的神经元周网（PNN）。PNN在关键期结束时限制可塑性方面发挥作用。在成年大鼠小脑中，PNN被发现在大的深小脑核（DCN）神经元和高尔基体神经元周围，并且由硫酸软骨素蛋白聚糖（CSPG）、腱生蛋白-R（TN-R）、透明质酸（HA）和连接蛋白（例如软骨连接蛋白1（Crtl 1））组成。颗粒细胞和浦肯野细胞被部分组织化的基质包围。被PNN包围的神经胶质细胞和神经元都是一些CSPG和TN-R的合成位点，但只有神经元产生HA合成酶（HAS），从而产生HA和连接蛋白，其是有组织基质的支架分子。为了阐明PNN的形成机制，我们通过免疫组织化学和原位杂交分析了PNN的成分在大鼠小脑出生后发育过程中的PNN形成过程中上调，以及哪些细胞类型表达它们。我们观察到紫藤花凝集素结合PNNs周围DCN神经元从出生后7天（P）和周围高尔基体神经元从P14。在PNN开始形成的同时，这些神经元上调聚集蛋白聚糖、Crtl 1和HASs mRNA。然而，Crtl 1是唯一的PNN组件被专门表达在周围的PNN神经元。在DCN中显示神经元周围网络模式的另一种连接蛋白Bral 2在发育后期上调。这些数据表明，聚集蛋白聚糖，HA，特别是Crtl 1可能是PNN初始组装的关键要素。
Extracellular matrix molecules accumulate around central nervous system neurons during postnatal development, forming so-called perineuronal nets (PNNs). PNNs play a role in restricting plasticity at the end of critical periods. In the adult rat cerebellum, PNNs are found around large, deep cerebellar nuclei (DCN) neurons and Golgi neurons and are composed of chondroitin sulfate proteoglycans (CSPGs), tenascin-R (TN-R), hyaluronan (HA), and link proteins, such as cartilage link protein 1 (Crtl1). Granule cells and Purkinje cells are surrounded by a partially organized matrix. Both glial cells and neurons surrounded by PNNs are the site of synthesis of some CSPGs and of TN-R, but only neurons produce HA synthetic enzymes (HASs), thus HA, and link proteins, which are scaffolding molecules for an organized matrix. To elucidate the mechanisms of formation of PNNs, we analyzed by immunohistochemistry and in situ hybridization which PNN components are upregulated during PNN formation in rat cerebellar postnatal development and what cell types express them. We observed that Wisteria floribunda agglutinin-binding PNNs develop around DCN neurons from postnatal day (P)7 and around Golgi neurons from P14. At the same time as their PNNs start to form, these neurons upregulate aggrecan, Crtl1, and HASs mRNAs. However, Crtl1 is the only PNN component to be expressed exclusively in neurons surrounded by PNNs. The other link protein that shows a perineuronal net pattern in the DCN, Bral2, is upregulated later during development. These data suggest that aggrecan, HA, and, particularly, Crtl1 might be crucial elements for the initial assembly of PNNs.