Treatment with progesterone after focal cerebral ischemia suppresses proliferation of progenitor cells but enhances survival of newborn neurons in adult male mice
Treatment with progesterone after focal cerebral ischemia suppresses proliferation of progenitor cells but enhances survival of newborn neurons in adult male mice
复制标题
局灶性脑缺血后用黄体酮治疗可抑制成年雄性小鼠祖细胞的增殖，但可提高新生神经元的存活率
DOI：
10.1016/j.neuropharm.2010.01.002
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发表时间：
2010-05-01
影响因子：
4.7
通讯作者：
Chen, Ling
中科院分区：
文献类型：
--
作者：
Zhang, Zhuo;Yang, Rong;Chen, Ling
中风刺激成年啮齿动物和人类心室下区（SVZ）和海马齿状回（DG）的细胞增殖。然而，大多数新生细胞会在1-2周内死亡。我们最近发现孕酮（P4）促进DG新生神经元的存活，改善脑缺血后的神经功能障碍。本研究旨在进一步探讨P4对大鼠DG、SVZ和纹状体缺血神经发生的影响。用溴脱氧尿苷（BrdU）标记大脑中动脉闭塞（MCAO）后第3天的增殖细胞。在BrdU-D-1（注射前1天至注射后1天）或BrdU-D4-6（注射后4-6天）连续3天注射P4 （4 mg/kg）。p4在BrdU- d -1 （to 1）处处理可减弱MCAO-DG和-SVZ中24 h龄BrdU（+）细胞密度的增加，这种增加被5 α -还原酶抑制剂非那雄胺阻断。P4对BrdU- d4 -6的处理显著增加了MCAO-DG中28日龄BrdU（+）细胞的密度，但没有改变BrdU(+)/NeuN（+）和BrdU(+)/GFAP（+）细胞的群体比例，这对P4受体和细胞外信号调节激酶（ERK）的阻断敏感。此外，p4对BrdU- d4 -6的处理使mcao纹状体中28日龄BrdU（+）细胞的密度增加了约2倍。这项研究提供了证据，表明中风后p4治疗抑制了缺血刺激的祖细胞增殖，但改善了缺血诱导的新生细胞的不良存活率。(C) 2010 Elsevier Ltd.版权所有。
Stroke stimulates cell proliferation in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG) in adult rodents and humans. However, most newborn cells will die within 1-2 weeks. We recently have revealed that progesterone (P4) promotes the survival of newborn neurons in the DG and improves the neurological dysfunction after cerebral ischemia. The aim of this study was to further explore the effects of P4 on the ischemia-induced neurogenesis in the DG, SVZ and striatum. Bromodeoxyuridine (BrdU) was used to label proliferating cells on day 3 after middle cerebral artery occlusion (MCAO). P4 (4 mg/kg) was injected for 3 consecutive days at BrdU-D-1 (to 1) (from one day before to one day after BrdU-injection) or BrdU-D4-6 (4-6 days after BrdU-injection). The P4-treatment at BrdU-D-1 (to 1) attenuated the increase in the density of 24-h-old BrdU(+) cells in MCAO-DG and -SVZ, which was blocked by the 5 alpha-reductase inhibitor finasteride. The P4-treatment at BrdU-D4-6 significantly increased the density of 28-day-old BrdU(+) cells in MCAO-DG without changing the population ratios of BrdU(+)/NeuN(+) and BrdU(+)/GFAP(+) cells, which was sensitive to the blockade of P4 receptor and extracellular signal-regulated kinase (ERK). In addition, the P4-treatment at BrdU-D4-6 produced approximately 2-fold increase in the density of 28-day-old BrdU(+) cells in MCAO-striatum. This study provides evidence that the P4-treatment after stroke suppresses ischemia-stimulated proliferation of progenitor cells but improves the poor survival of ischemia-induced newborn cells. (C) 2010 Elsevier Ltd. All rights reserved.