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颈动脉体中的神经源性微环境及其在抗帕金森病细胞治疗中的适用性。

The neurogenic niche in the carotid body and its applicability to antiparkinsonian cell therapy.

作者信息

López-Barneo José, Pardal Ricardo, Ortega-Sáenz Patricia, Durán Rocío, Villadiego Javier, Toledo-Aral Juan José

机构信息

Instituto de Biomedicina de Sevilla, Edificio de Laboratorios, 2a planta, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Avenida Manuel Siurot s/n, 41013 Seville, Spain.

出版信息

J Neural Transm (Vienna). 2009 Aug;116(8):975-82. doi: 10.1007/s00702-009-0201-5. Epub 2009 Mar 5.

Abstract

The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial O(2) tension to elicit hyperventilation during hypoxia. The CB is composed of clusters of neuron-like glomus, or type I, cells that are highly dopaminergic and contain large amounts of the glial cell line-derived neurotrophic factor (GDNF). Glomus cells are enveloped by glia-like sustentacular, or type II, cells. In chronic hypoxia the CB grows with increase in glomus cell number. This adaptive response depends on a collection of neural progenitors that can be isolated and induced to form clonal neurospheres in vitro. CB neurospheres contain numerous newly differentiated glomus cells, which maintain their functional properties and the ability to synthesize dopamine and GDNF. Intrastriatal CB transplants have been assayed in animal models of Parkinson's disease (PD) to test whether they increase the striatal dopamine levels and/or exert a neuroprotective action on the nigrostriatal pathway. Two pilot safety studies performed on PD patients subjected to CB autotransplantation have suggested that a major limitation of this technique is the small size of the organ. This could, however, be overcome by the in vitro formation of new CB tissue derived from adult CB stem cells.

摘要

颈动脉体(CB)是一种源自神经嵴的器官,其主要功能是感知动脉血氧张力的变化,以便在缺氧时引发过度通气。颈动脉体由神经元样的球细胞(即I型细胞)簇组成,这些细胞具有高度的多巴胺能特性,并含有大量的胶质细胞源性神经营养因子(GDNF)。球细胞被胶质样的支持细胞(即II型细胞)所包裹。在慢性缺氧状态下,颈动脉体随着球细胞数量的增加而生长。这种适应性反应依赖于一群神经祖细胞,这些细胞可以在体外被分离并诱导形成克隆性神经球。颈动脉体神经球包含大量新分化的球细胞,这些球细胞保持其功能特性以及合成多巴胺和GDNF的能力。在帕金森病(PD)动物模型中对纹状体内颈动脉体移植进行了检测,以测试其是否能提高纹状体多巴胺水平和/或对黑质纹状体通路发挥神经保护作用。对接受颈动脉体自体移植的帕金森病患者进行的两项初步安全性研究表明,该技术的一个主要限制是器官体积小。然而,这可以通过体外从成年颈动脉体干细胞形成新的颈动脉体组织来克服。

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