Impaired neural stem/progenitor cell proliferation in streptozotocin-induced and spontaneous diabetic mice
Impaired neural stem/progenitor cell proliferation in streptozotocin-induced and spontaneous diabetic mice
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DOI：
10.1016/j.neures.2010.08.012
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发表时间：
2010-12-01
影响因子：
2.9
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Guo, Jun;Yu, Caiyong;Wang, Jian
糖尿病与包括大脑在内的许多器官系统的不良并发症有关。越来越多的证据表明，糖尿病，无论其类型，损害成年海马齿状回（DG）的神经发生（HPC）。然而，这种疾病对室管膜下区（SVZ）神经发生的影响还没有得到很好的证实。我们在雄性NOD/SCID（非肥胖糖尿病/严重联合免疫缺陷）小鼠和C57 BL/6小鼠中诱导糖尿病，单次腹腔注射链脲佐菌素（STZ）。在STZ注射后第7天或第21天，小鼠接受胸苷类似物5-溴-2 '-脱氧尿苷（BrdU）用于标记增殖细胞。24小时后处死小鼠，并用抗BrdU抗体对脑冠状切片进行染色。神经干/祖细胞（NSC/NPC）的增殖，所揭示的BrdU标记的细胞，显着减少在颗粒下区的DG在STZ治疗的糖尿病小鼠。在SVZ中观察到NSC/NPC增殖的类似减少。减少DG和SVZ细胞增殖也被发现在糖尿病NOD小鼠，自发性糖尿病的模型，和减少被衰减双侧肾上腺切除术（Adx）。在糖尿病前期或糖尿病NOD小鼠中，Adx没有改变血糖或胰岛素水平，但Adx部分增加了海马和SVZ脑源性神经营养因子（BDNF）的mRNA水平，BDNF是NSC/NPC增殖的关键调节因子。此外，NOD和NOD/SCID小鼠显示出比C57 BL/6小鼠更快地减少NSC/NPC增殖以响应糖尿病。因此，我们得出结论，糖尿病抑制SVZ和HPC的细胞增殖，抑制与糖皮质激素水平升高和BDNF表达减少。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Diabetes mellitus is associated with adverse complications in many organ systems including the brain. Accumulating evidence indicates that diabetes, regardless of its type, impairs adult neurogenesis in the dentate gyrus (DG) of the hippocampus (HPC). However, the effects of the disease on neurogenesis in the subventricular zone (SVZ) are not well established. We induced diabetes in male NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice and C57BL/6 mice with a single intraperitoneal injection of streptozotocin (STZ). On day 7 or day 21 after STZ injection mice received the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) for labeling of proliferative cells. Mice were sacrificed 24 h later and brain coronal sections were stained with anti-BrdU antibodies. Neural stem/progenitor cell (NSC/NPC) proliferation, as revealed by BrdU-labeled cells, was markedly decreased in the subgranular zone of the DG in STZ-treated diabetic mice. A similar reduction of NSC/NPC proliferation was seen in the SVZ. Reduced DG and SVZ cell proliferation was also found in diabetic NOD mice, a model of spontaneous diabetes, and the reduction was attenuated by bilateral adrenalectomy (Adx). Adx did not alter blood glucose or insulin levels in either prediabetic or diabetic NOD mice, but Adx partly increased mRNA levels of hippocampal and SVZ brain-derived neurotrophic factor (BDNF), a crucial regulator of NSC/NPC proliferation. Moreover, NOD and NOD/SCID mice showed a more rapid reduction of NSC/NPC proliferation than C57BL/6 mice in response to diabetes. Thus, we conclude that diabetes inhibits cell proliferation in both the SVZ and HPC, and inhibition was associated with elevated glucocorticoid levels and reduced BDNF expression. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.