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成年松鼠猴的吻侧迁移流:新生神经元对嗅结节的贡献及抗凋亡蛋白Bcl-2的作用

The rostral migratory stream in adult squirrel monkeys: contribution of new neurons to the olfactory tubercle and involvement of the antiapoptotic protein Bcl-2.

作者信息

Bédard Andréanne, Lévesque Martin, Bernier Patrick J, Parent André

机构信息

Centre de recherche Université Laval Robert-Giffard, 2601, de la Canardière, Local F-6500, Beauport, Québec, Canada, G1J 2G3.

出版信息

Eur J Neurosci. 2002 Nov;16(10):1917-24. doi: 10.1046/j.1460-9568.2002.02263.x.

Abstract

The subventricular zone (SVZ) lying along the ependymal layer of lateral ventricle is known to generate neural progenitor cells throughout adulthood in specific areas of the mammalian brain. In rodents, the anterior region of the SVZ produces neuroblasts that migrate in chain toward the olfactory bulb along the so-called rostral migratory stream (RMS). In the present study, the organization of the RMS in a representative of New World primates - the squirrel monkey (Saimiri sciureus) - was studied by using bromodeoxyuridine (BrdU), a thymidine analogue that incorporates itself into the DNA of cells undergoing mitotic division. Double and triple immunofluorescence labelling with a confocal microscope served to visualize cells that expressed BrdU as well as molecular markers of neurogenesis. Numerous newborn (BrdU+) cells, many ensheated in glial (GFAP+) tubes, were scattered along the entire RMS in squirrel monkeys. Some of these BrdU+ cells expressed molecular markers for early committed neurons (TuJ1), postmitotic granular neuroblasts (TUC-4) or mature neurons (MAP-2, NeuN), and virtually all of them expressed the antiapoptotic protein Bcl-2. A significant number of BrdU+ cells were found to deviate from the main stream of the RMS. Instead of reaching the olfactory bulb, these cells migrated ventrally into the olfactory tubercle, where they expressed a mature neuronal phenotype (MAP-2). These findings reveal that the RMS in New World monkeys is mitotically robust and markedly extended and suggest that Bcl-2 might play a role in the survival and/or differentiation of newborn neurons destined to olfactory bulb and olfactory tubercle in primates.

摘要

脑室下区(SVZ)沿侧脑室室管膜层分布,已知在成年哺乳动物大脑的特定区域可产生神经祖细胞。在啮齿动物中,SVZ的前部产生神经母细胞,这些神经母细胞沿着所谓的嘴侧迁移流(RMS)呈链状向嗅球迁移。在本研究中,利用溴脱氧尿苷(BrdU)对一种新大陆灵长类动物——松鼠猴(Saimiri sciureus)的RMS组织结构进行了研究,BrdU是一种胸腺嘧啶类似物,可掺入进行有丝分裂的细胞的DNA中。通过共聚焦显微镜进行双重和三重免疫荧光标记,以可视化表达BrdU以及神经发生分子标记的细胞。在松鼠猴的整个RMS中,散布着许多新生(BrdU+)细胞,其中许多被包裹在神经胶质(GFAP+)管中。这些BrdU+细胞中的一些表达早期定向神经元(TuJ1)、有丝分裂后颗粒神经母细胞(TUC-4)或成熟神经元(MAP-2、NeuN)的分子标记,并且几乎所有细胞都表达抗凋亡蛋白Bcl-2。发现大量BrdU+细胞偏离RMS的主流。这些细胞没有到达嗅球,而是向腹侧迁移到嗅结节,在那里它们表达成熟的神经元表型(MAP-2)。这些发现表明,新大陆猴的RMS有强大的有丝分裂能力且明显延长,这表明Bcl-2可能在灵长类动物中注定要迁移到嗅球和嗅结节的新生神经元的存活和/或分化中发挥作用。

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