Lovell Mark A, Geiger Hartmut, Van Zant Gary E, Lynn Bert C, Markesbery William R
Sanders-Brown Center on Aging and Alzheimer's Disease Research Center, 800 S. Limestone St., 101 Sanders-Brown Bldg., University of Kentucky, Lexington, KY 40536-0230, USA.
Neurobiol Aging. 2006 Jul;27(7):909-17. doi: 10.1016/j.neurobiolaging.2005.05.004. Epub 2005 Jun 23.
Recent studies demonstrate that isolated neural precursor cells are capable of generating neurons, astrocytes, and oligodendrocytes from neurogenic regions of adult brain. Because these studies use surgically resected or fresh postmortem specimens from young subjects, it is not clear whether neural precursor cells remain in the brain of normal aged subjects or subjects with Alzheimer's disease (AD). The purpose of this study was to determine if viable precursor cells remain in aged control and AD brain. AD subjects have significantly fewer viable precursor cells in the hippocampus compared with age-matched normal control subjects. Musashi-1 and Ki-67-positive precursor cells from AD self renew, but reach senescence earlier than cells isolated from normal aged control subjects. Precursor cells from AD and aged normal control specimens can differentiate into tubulin- and Tuj-1-positive neurons and GFAP-positive astrocytes. This study demonstrates that viable precursor cells remain in AD and aged normal control brain specimens and can be induced to differentiate. These results raise the possibility of stimulation of inherent precursor cells of aged individuals or AD patients to replace neurons lost in aging and/or neurodegeneration.
近期研究表明，分离出的神经前体细胞能够从成年大脑的神经发生区域生成神经元、星形胶质细胞和少突胶质细胞。由于这些研究使用的是来自年轻受试者的手术切除标本或新鲜尸检标本，因此尚不清楚正常老年受试者或阿尔茨海默病（AD）患者的大脑中是否仍存在神经前体细胞。本研究的目的是确定在老年对照和AD大脑中是否存在存活的前体细胞。与年龄匹配的正常对照受试者相比，AD受试者海马体中存活的前体细胞明显更少。来自AD的Musashi-1和Ki-67阳性前体细胞能够自我更新，但比从正常老年对照受试者分离出的细胞更早进入衰老状态。来自AD和老年正常对照标本的前体细胞可分化为微管蛋白和Tuj-1阳性神经元以及GFAP阳性星形胶质细胞。本研究表明，存活的前体细胞存在于AD和老年正常对照脑标本中，并且可以被诱导分化。这些结果增加了刺激老年个体或AD患者固有前体细胞以替代衰老和/或神经退行性变中丢失的神经元的可能性。
