ApoE Regulates the Development of Adult Newborn Hippocampal Neurons.
ApoE Regulates the Development of Adult Newborn Hippocampal Neurons.
复制标题
DOI：
10.1523/eneuro.0155-18.2018
复制
发表时间：
2018-07
期刊：
影响因子：
3.4
通讯作者：
Kernie SG
中科院分区：
文献类型：
--
作者：
Tensaouti Y;Stephanz EP;Yu TS;Kernie SG
成人海马神经发生发生在整个生命过程中，并被认为参与认知功能，如学习和记忆。已经确定了许多调节成年海马神经发生的基因，尽管其中大多数与祖细胞增殖和存活有关，但与发育成完全分化的神经元无关。在这些基因中，载脂蛋白E（ApoE）是特别引人注目的，因为人类ApoE亚型E4是阿尔茨海默病发展的风险因素，据报道海马神经发生功能障碍。为了研究ApoE及其人亚型对成年海马神经发生和神经元发育的影响，将携带GFP表达载体的逆转录病毒注射到野生型（WT）、ApoE缺陷型和人靶向置换（ApoE 3和ApoE 4）小鼠中，以感染齿状回中的祖细胞，并分析完全发育的GFP表达神经元的形态。对这些成年神经元的分析显示，与WT小鼠相比，ApoE缺陷小鼠的树突状分支和棘密度的复杂性显著降低，与ApoE 3相比，ApoE 4小鼠的树突状分支和棘密度也显著降低。这些研究结果表明，ApoE缺乏和ApoE 4人类亚型都损害海马神经发生，并提供洞察ApoE如何影响海马相关的神经系统疾病。
Adult hippocampal neurogenesis occurs throughout life and is believed to participate in cognitive functions such as learning and memory. A number of genes that regulate adult hippocampal neurogenesis have been identified, although most of these have been implicated in progenitor proliferation and survival, but not in the development into fully differentiated neurons. Among these genes, apolipoprotein E (ApoE) is particularly compelling because the human ApoE isoform E4 is a risk factor for the development of Alzheimer’s disease, where hippocampal neurogenesis is reported to be dysfunctional. To investigate the effects of ApoE and its human isoforms on adult hippocampal neurogenesis and neuronal development, retroviruses carrying a GFP-expressing vector were injected into wild-type (WT), ApoE-deficient, and human targeted replacement (ApoE3 and ApoE4) mice to infect progenitors in the dentate gyrus and analyze the morphology of fully developed GFP-expressing neurons. Analysis of these adult-born neurons revealed significant decreases in the complexity of dendritic arborizations and spine density in ApoE-deficient mice compared with WT mice, as well as in ApoE4 mice compared with ApoE3. These findings demonstrate that ApoE deficiency and the ApoE4 human isoform both impair hippocampal neurogenesis and give insight into how ApoE may influence hippocampal-related neurological diseases.