proNGF Inhibits Neurogenesis and Induces Glial Activation in Adult Mouse Dentate Gyrus
proNGF Inhibits Neurogenesis and Induces Glial Activation in Adult Mouse Dentate Gyrus
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proNGF 抑制成年小鼠齿状回的神经发生并诱导神经胶质激活
DOI：
10.1007/s11064-013-1071-7
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发表时间：
2013-08-01
影响因子：
4.4
通讯作者：
Liao, Hong
中科院分区：
文献类型：
--
作者：
Guo, Jingjing;Wang, Jianing;Liao, Hong
最近的研究表明，在衰老的大脑和阿尔茨海默氏病患者的大脑中，神经生长因子（PRONGF）的前体高度升高。 Prongf积累在海马，这是与学习和记忆有关的重要神经源区域。但是，尚不清楚Prongf是否对海马神经发生有影响。在这项研究中，我们证明了PRONGF的高亲和力受体P75神经营养因子（P75NTR），在小鼠海马中的细胞和有丝分裂后成熟细胞的细胞上表达。 PRONGF注入成年小鼠海马可显着降低BRDU结合细胞的密度和海马亚颗粒下BRDU/Doublecortin双阳性细胞的密度，表明Prongf对海马神经发生的抑制作用。 PRONGF输注还诱导明显的细胞凋亡，并活化的住宅星形胶质细胞和小胶质细胞，这可能会进一步损害海马神经发生。这些结果表明，PRONGF在调节海马神经发生中发挥了关键作用，并可能解释了记忆缺陷和认知障碍。
Recent studies have shown that the precursor of nerve growth factor (proNGF) is highly elevated in aging brains and in the brains of patients with Alzheimer's Disease. proNGF accumulates in hippocampus which is an important neurogenic region related to learning and memory. However, it remains unclear whether proNGF has an influence on hippocampal neurogenesis. In this study, we demonstrated that the high-affinity receptor of proNGF, p75 neurotrophic factor (p75NTR), was expressed both on cells undergoing mitosis and postmitotic mature cells in mouse hippocampus. proNGF infusion into adult mouse hippocampus significantly reduced the density of BrdU-incorporating cells and the density of BrdU/Doublecortin double positive cells in the subgranular zone of hippocampus, indicating an inhibitory effect of proNGF on hippocampal neurogenesis. proNGF infusion also induced prominent cell apoptosis and activated residential astrocyte and microglia, which might further impair the hippocampal neurogenesis. These results implied that proNGF played a pivotal role in regulating the hippocampal neurogenesis and might account for the memory deficit and cognitive impairment.