Institute of Biology II, Universität Leipzig, Leipzig, Germany.
Hippocampus. 2010 Aug;20(8):971-9. doi: 10.1002/hipo.20693.
Besides its role in Alzheimer's disease, the amyloid precursor protein (APP) is implicated in several physiological functions in neuronal tissue such as cell survival, neurite outgrowth, synaptic formation, and neuronal plasticity. The present study analyzed effects of human wild-type APP (hAPP) overexpression on adult hippocampal neurogenesis in transgenic mice. Mice were housed under either standard or enriched conditions, the latter to boost neurogenetic activity. Different aspects of neurogenesis including proliferation, survival, and differentiation were assessed by employing the BrdU-incorporation method and, in parallel, immunohistochemistry for the neuronal and glial markers NeuN and S100b, respectively. Overexpression of hAPP caused a significant decrease in cell proliferation under standard housing conditions. The relative increase in the proliferation rate following housing in enriched environment was not different to that observed in wild-type mice. Overexpression of hAPP, on the other hand, promoted the survival of newly generated cells, but just under conditions of standard housing. Findings further suggest that overexpression of hAPP suppresses the phenotypic shift toward neuronal differentiation under conditions of enriched environment. In summary, the results reveal a dual effect of APP on adult hippocampal neurogenesis, comprising antiproliferative and prosurvival activities.
除了在阿尔茨海默病中的作用外，淀粉样前体蛋白 (APP) 还涉及神经元组织中的几种生理功能，如细胞存活、突起生长、突触形成和神经元可塑性。本研究分析了人野生型 APP (hAPP) 过表达对转基因小鼠成年海马神经发生的影响。将小鼠分别饲养在标准或丰富环境中，后者可促进神经发生活性。通过 BrdU 掺入法评估神经发生的不同方面，包括增殖、存活和分化，并平行进行神经元标志物 NeuN 和神经胶质标志物 S100b 的免疫组织化学染色。在标准饲养条件下，hAPP 的过表达导致细胞增殖显著减少。在丰富环境中饲养后的增殖率相对增加与野生型小鼠观察到的增加没有差异。另一方面，hAPP 的过表达促进了新生成细胞的存活，但仅在标准饲养条件下。研究结果进一步表明，hAPP 的过表达抑制了在丰富环境条件下向神经元分化的表型转变。总之，结果揭示了 APP 对成年海马神经发生的双重影响，包括抗增殖和促进存活的作用。
