Department of Anatomy With Radiology, University of Auckland, Private Bag 92019, 85 Park Road, Grafton, Auckland, New Zealand.
Neuroscience. 2011 Dec 29;199:577-88. doi: 10.1016/j.neuroscience.2011.09.010. Epub 2011 Sep 14.
Increases in cell proliferation in the hippocampus have been robustly demonstrated in animal models of neurodegenerative diseases like Huntington's disease (HD). However, in the subventricular zone, animal models of HD have demonstrated no change in cell proliferation compared to wild types, while in humans there is a distinct increase in cell proliferation in HD cases. Interestingly, there have been no reports on cell proliferation in the human subgranular zone (SGZ) of the hippocampus in HD, despite numerous transgenic mouse models of HD showing decreased proliferation in the SGZ. Furthermore, HD can be divided into those with mainly mood and mainly motor symptomatology. We hypothesized that HD cases with mainly mood symptomatology would show a greater change in hippocampal proliferation, which has previously been implicated in mood disorders such as depression. Therefore, in the current study we examined and compared proliferation in the SGZ in normal vs. HD, HD mood, and HD motor affected cases. However, our results revealed no significant differences in SGZ proliferation between normal and HD cases, and no differences when divided into groups based on mood and motor symptomatology. Our results were confirmed using a range of cell-cycle protein markers and, overall, were comparable with previous studies of the human hippocampus, where very little proliferation was detected in the adult SGZ. These results demonstrate that in humans the SGZ is far less proliferative than the SVZ, and suggests that hippocampal plasticity in humans does not primarily involve cell proliferation.
在亨廷顿病 (HD) 等神经退行性疾病的动物模型中，已经强有力地证明了海马体中的细胞增殖增加。然而，在脑室下区，与野生型相比，HD 的动物模型并未显示细胞增殖发生变化，而在人类中，HD 病例中细胞增殖明显增加。有趣的是，尽管有许多 HD 的转基因小鼠模型显示脑室下区 (SVZ) 的增殖减少，但在 HD 中，人类海马体的 SVZ 细胞增殖尚无报道。此外，HD 可以分为主要表现为情绪和主要表现为运动症状的两种类型。我们假设，主要表现为情绪症状的 HD 病例的海马体增殖会发生更大的变化，因为之前的研究表明，情绪障碍如抑郁症与海马体的增殖有关。因此，在目前的研究中，我们检查和比较了正常对照组与 HD、HD 情绪障碍和 HD 运动障碍组的 SVZ 增殖情况。然而，我们的结果显示，SVZ 增殖在正常对照组和 HD 病例组之间没有显著差异，也没有根据情绪和运动症状进行分组时的差异。我们的结果使用了一系列细胞周期蛋白标志物进行了验证，总的来说，与人类海马体的先前研究结果相当，在成年 SVZ 中检测到的增殖非常少。这些结果表明，在人类中，SVZ 的增殖能力远低于 SVZ，这表明人类的海马体可塑性并不主要涉及细胞增殖。
