Department of Histology and Embryology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Simkova 870, P.O. Box 38, 500 38 Hradec Králové, Czech Republic.
CNS Neurol Disord Drug Targets. 2011 Jun;10(4):486-99. doi: 10.2174/187152711795563967.
The evidence for the existence of neurogenesis in the adult mammalian brain, including humans is now widely accepted. Despite the fact that adult neural stem cells appear to be very promising, a wide range of their unrevealed properties, abilities but also limitations under physiological and especially pathological conditions still need to be investigated and explained. Huntington's disease (HD) is characterized by successive degeneration of relatively well-defined neuronal population. Moreover, the most affected region, the caudate nucleus, is adjacent to the subependymal zone (SEZ) neurogenic region. Therefore, the possibility to harness the endogenous neural stem cell capacity for repairing, or at least restricting, the fatal neurodegenerative process in HD patients using promoted neurogenesis in the adult SEZ represent the exciting new possibility in clinical management of this disorder. On the other hand, many questions have to be answered before neuronal replacement therapies using endogenous precursors become a reality, particularly in relation to neurodegenerative diseases. Fundamental for all experimental, functional and future clinical studies is detailed morphological description of structures involved in the process of neurogenesis. The objectives of this review are to describe neurogenesis in the adult murine and human brain (with particular emphasis to morphological aspects of this process) and to determine to what extent it is affected in animal models of HD and in the human HD brain. Due to very limited evidence referring to the impact of striatal pathology of HD phenotype on the adult neurogenesis in the SEZ, some results gained from our studies on two rat models of HD, i.e. the neurotoxic lesion and transgenic HD rats, and on human HD brains are discussed.
成人哺乳动物大脑（包括人类）中存在神经发生的证据现在已被广泛接受。尽管成年神经干细胞似乎非常有前途，但它们在生理和特别是病理条件下的许多未被揭示的特性、能力以及局限性仍需要进行研究和解释。亨廷顿病（HD）的特征是相对明确的神经元群体的连续退化。此外，受影响最严重的区域——尾状核——紧邻室下区（SEZ）神经生成区。因此，利用成年 SEZ 中促进的神经发生来利用内源性神经干细胞的能力来修复，或至少限制 HD 患者致命的神经退行性过程，代表了这种疾病临床管理的令人兴奋的新可能性。另一方面，在神经元替代疗法成为现实之前，还有许多问题需要回答，特别是在涉及神经退行性疾病方面。所有实验、功能和未来临床研究的基础都是对参与神经发生过程的结构进行详细的形态描述。这篇综述的目的是描述成年鼠和人类大脑中的神经发生（特别强调这个过程的形态学方面），并确定它在 HD 动物模型和人类 HD 大脑中受到了多大程度的影响。由于与 HD 表型纹状体病理学对 SEZ 中成年神经发生的影响相关的证据非常有限，因此讨论了一些我们在两种 HD 大鼠模型（即神经毒性损伤和转基因 HD 大鼠）和人类 HD 大脑上的研究结果。
