Kanaumi Takeshi, Milenkovic Ivan, Adle-Biassette Homa, Aronica Eleonora, Kovacs Gabor G
Institute of Neurology, Medical University of Vienna, Vienna A-1090, Austria; Department of Pediatrics, Nakatsu Municipal Hospital, Nakatsu 871-8511, Japan; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Int J Dev Neurosci. 2013 Dec;31(8):796-803. doi: 10.1016/j.ijdevneu.2013.09.011. Epub 2013 Oct 7.
Down syndrome (DS), the most common genetic cause of mental retardation, is characterized by reduced number of neurons and delayed myelination. Though non-neuronal cells in the brain are vital for the development, survival, and function of neurons, there is a paucity of comparative studies of normal development and DS, in particular in the temporal lobe, a region of interest for cognitive decline. We evaluated immunoreactivity for CD68 (macrophage), HLA-DR (microglia), Olig2 and TPPP/p25 (oligodendroglia), and GFAP (astroglia) in the germinal matrix (GM), temporal lobe white matter (TeWM) and hippocampus from 14 weeks of gestations to newborn in 28 DS patients and 30 age-matched controls. The rate of increase of CD68 positive cells in the GM, CA1 hippocampal subregion and subiculum was significantly higher in DS. The density of Olig2 positive cells in the GM was lower in DS brains at early stages, then showed a transient increase contrasting controls. Olig2 expression increased more in the TeWM in DS, suggesting an altered pattern of oligodendrocyte progenitor generation. GFAP-immunoreactivity in DS was significantly lower in the middle pregnancy period in the TeWM and did not increase between early and middle periods in the GM compared to controls, likely reflecting a defect in astrocyte production. The altered expression of non-neuronal cell markers during normal development and DS may play a role in, or reflect, defective neurogenesis, leading to reduced number of neurons and delayed myelination in the developing DS brain. This has implications for the understanding of the mental retardation in DS patients.
唐氏综合征（DS）是智力发育迟缓最常见的遗传病因，其特征为神经元数量减少和髓鞘形成延迟。尽管大脑中的非神经元细胞对神经元的发育、存活和功能至关重要，但对正常发育和DS进行比较研究的却很少，尤其是在颞叶，这是一个与认知衰退相关的区域。我们评估了28例DS患者和30例年龄匹配对照从妊娠14周直至新生儿期的生发基质（GM）、颞叶白质（TeWM）和海马中CD68（巨噬细胞）、HLA - DR（小胶质细胞）、Olig2和TPPP/p25（少突胶质细胞）以及GFAP（星形胶质细胞）的免疫反应性。DS患者GM、海马CA1亚区和海马下托中CD68阳性细胞的增加速率显著更高。早期DS大脑GM中Olig2阳性细胞密度较低，随后与对照组相比出现短暂增加。DS患者TeWM中Olig2表达增加更多，表明少突胶质细胞祖细胞生成模式改变。与对照组相比，DS患者TeWM在妊娠中期的GFAP免疫反应性显著降低，且GM在早期和中期之间未增加，这可能反映了星形胶质细胞生成的缺陷。正常发育和DS过程中非神经元细胞标志物表达的改变可能在有缺陷的神经发生中起作用或反映这种情况，导致发育中的DS大脑神经元数量减少和髓鞘形成延迟。这对于理解DS患者的智力发育迟缓具有重要意义。
