Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPsw,lnd)mice
Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPsw,lnd)mice
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DOI：
10.1073/pnas.0403678101
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发表时间：
2004-09-07
影响因子：
11.1
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
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作者：
Jin, KL;Galvan, V;Greenberg, DA
神经发生在成人大脑中继续，并在某些病理状态下增加。我们最近报道了阿尔茨海默病（AD）患者海马神经发生增强。我们现在报告，AD对神经发生的影响可以在转基因小鼠模型中重现。表达瑞典和印第安纳州淀粉样前体蛋白突变的PDGF-APP（Sw，Ind）小鼠在两个神经增殖区域（齿状回和脑室下区）显示BrdUrd掺入增加和未成熟神经元标记物表达增加。这些变化，包括BrdUrd标记细胞数量增加约2倍，在3个月大时观察到，此时未检测到神经元损失和淀粉样蛋白沉积。由于AD和AD动物模型中神经发生增强，因此它似乎是由疾病本身引起的，而不是由混淆的临床因素引起的。由于PDGF-APP（Sw，Ind）小鼠在没有神经元损失的情况下神经发生增加，因此它必须由更微妙的疾病表现（如神经传递受损）触发。AD和AD动物模型中神经发生的增强表明神经发生可能是一种代偿反应，进一步增强神经发生的措施可能具有治疗潜力。
Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APP(Sw,Ind) mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of approximate to2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APP(Sw,Ind) mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.