Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
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DOI：
10.1002/cne.1040
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发表时间：
2001-07-09
影响因子：
2.5
通讯作者：
McKay, RDG
中科院分区：
文献类型：
--
作者：
Cameron, HA;McKay, RDG
了解新颗粒细胞向成人齿状回添加的速率对于理解成人神经发生的功能至关重要。尽管对成人齿状回的神经发生进行了大量的研究，但关于这一现象的严重性的基本问题从未得到解决。s期标记物溴脱氧尿苷（BrdU）在最近的成人神经发生研究中被广泛使用，但它只在胚胎脑中进行了仔细的测试。在这里，我们发现高剂量BrdU （300 mg/kg）是成年大鼠齿状回分裂细胞的特异性、定量和无毒标记物，而低剂量BrdU仅标记一小部分s期细胞。通过使用这种高剂量的BrdU和第二种s期标记物[H-3]胸苷，我们发现年轻的成年大鼠有9400个分裂细胞增殖，细胞周期为25小时，每天产生9000个新细胞，或每月超过25万个。在BrdU注射5-12天内，可以用神经元特异性抗体TuJ1和TUC-4鉴定出大量未成熟颗粒神经元，占齿状回所有BrdU标记细胞的50%。每月产生的新颗粒神经元数量占颗粒细胞群总大小的6%，占传入和传出细胞群大小的30-60% （West et al. [1991] Anat Rec 231:482-497; Mulders et al. [1997] J Comp Neurol 385:83-94）。大量的成体颗粒细胞支持了这些新神经元在海马功能中起重要作用的观点。出版于2001年Wiley-Liss， Inc.（匕首）。
Knowing the rate of addition of new granule cells to the adult dentate gyrus is critical to understanding the function of adult neurogenesis. Despite the large number of studies of neurogenesis in the adult dentate gyrus, basic questions about the magnitude of this phenomenon have never been addressed. The S-phase marker bromodeoxyuridine (BrdU) has been extensively used in recent studies of adult neurogenesis, but it has been carefully tested only in the embryonic brain. Here, we show that a high dose of BrdU (300 mg/kg) is a specific, quantitative, and nontoxic marker of dividing cells in the adult rat dentate gyrus, whereas lower doses label only a fraction of the S-phase cells. By using this high dose of BrdU along with a second S-phase marker, [H-3]thymidine, we found that young adult rats have 9,400 dividing cells proliferating with a cell cycle time of 25 hours, which would generate 9,000 new cells each day, or more than 250,000 per month. Within 5-12 days of BrdU injection, a substantial pool of immature granule neurons, 50% of all BrdU-labeled cells in the dentate gyrus, could be identified with neuron-specific antibodies TuJ1 and TUC-4. This number of new granule neurons generated each month is 6% of the total size of the granule cell population and 30-60% of the size of the afferent and efferent populations (West et al. [1991] Anat Rec 231:482-497; Mulders et al. [1997] J Comp Neurol 385:83-94). The large number of the adult-generated granule cells supports the idea that these new neurons play an important role in hippocampal function. Published 2001 Wiley-Liss, Inc.(dagger).