Dentate gyrus neurogenesis after cerebral ischemia and behavioral training.

Dentate gyrus neurogenesis after cerebral ischemia and behavioral training.
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DOI:
10.1177/1099800404271328
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发表时间:
2005-01-01
影响因子:
2.5
通讯作者:
Wadowska, Magdalena
Wadowska, Magdalena
中科院分区:
医学4区
文献类型:
--
作者:
Briones, Teresita L;Suh, Eugene;Wadowska, Magdalena

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哺乳动物大脑中的神经发生持续整个成年期。多种因素已被证明会影响神经发生,包括复杂环境经历 (EC)、运动 (EX) 和缺血性损伤。作者研究了短暂性全脑缺血后行为康复训练对齿状回中新细胞数量的影响,这些新细胞掺入了溴脱氧尿苷 (BrdU),这是一种胸苷类似物,可标记正在进行 DNA 复制的细胞。该研究纳入了 72 只动物,采用 4 支血管闭塞诱导脑缺血,而对照动物仅接受麻醉和假手术。手术后 3 天内,大鼠被随机分配到 EC、EX 或对照组(标准实验室条件下配对饲养)组。行为训练后两周处死所有动物。免疫组织化学结果显示,在所有缺血组以及 EC 和 EX 假手术组中,齿状回颗粒下区中 BrdU 标记的细胞数量增加,但没有看到显着的组间差异。细胞表型检查表明,在所有动物中,几乎所有 BrdU 阳性细胞都与 TuJ1(一种未成熟神经元标记物)共标记,而只有少数 BrdU 阳性细胞与 NeuN(一种成熟神经元标记物)共标记。 BrdU/NeuN 标记的细胞仅在假手术组和缺血 EC 组中可见。没有新细胞显示神经胶质原纤维酸性蛋白、星形胶质细胞标记、共标记。这些结果表明,成人大脑在受到损伤后具有固有的再生能力,并且损伤后的行为训练不会对神经发生产生附加作用。最后,在 EC 大鼠中观察到的 BrdU 阳性细胞的加速成熟可能是受到环境因素的调节。
Neurogenesis in the mammalian brain continues throughout adulthood. Several factors have been shown to influence neurogenesis, including experience in a complex environment (EC), exercise (EX), and ischemic insult. The authors investigated the effects of behavioral rehabilitation training following transient global cerebral ischemia on the number of new cells in the dentate gyrus that incorporated bromodeoxyuridine (BrdU), a thymidine analog that labels cells undergoing DNA replication. Seventy-two animals were included in the study, and 4-vessel occlusion was used to induce cerebral ischemia while control animals were subjected to anesthesia and sham surgery alone. Within 3 days of surgery, rats were randomly assigned to either EC, EX, or control (paired housing in standard laboratory conditions) groups. All animals were sacrificed 2 weeks after behavioral training. Immunohistochemistry results showed an increased number of BrdU-labeled cells in the subgranular zone of the dentate gyrus in all ischemic groups and in the EC and EX sham groups, although no significant group differences were seen. Examination of cell phenotype showed that almost all BrdU-positive cells colabeled with TuJ1, an immature neuron marker, in all animals whereas only a few BrdU-positive cells colabeled with NeuN, a mature neuron marker. BrdU/NeuN-labeled cells were seen only in the sham and ischemia EC groups. No new cells showed glial fibrillary acidic protein, astrocyte marker, colabeling. These results suggest that the adult brain has an inherent regenerative capacity after insult and that behavioral training following injury does not have an additive effect on neurogenesis. Finally, the enhanced maturation of BrdU-positive cells seen in the EC rats is probably modulated by environmental cues.