Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects
Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects
复制标题
Foxg1 的破坏会损害神经可塑性，导致社交和认知行为缺陷
DOI：
10.1186/s13041-019-0484-x
复制
发表时间：
2019-06-28
期刊：
影响因子：
3.6
通讯作者：
Zhao, Chunjie
中科院分区：
文献类型：
--
作者：
Yu, Baocong;Liu, Junhua;Zhao, Chunjie
已知转录因子Foxg 1在端脑的成熟神经元中持续高水平表达，但对其在神经可塑性中的作用知之甚少。人类FOXG 1基因突变导致学习记忆障碍和社交能力受限，被定义为FOXG 1综合征，但其致病机制尚不清楚。为了研究Foxg 1在成年人中的作用，我们将Camk 2a-Cre（ER）与Foxg 1（fl/fl）小鼠杂交，并在成熟神经元中用他莫昔芬有条件地破坏Foxg 1。我们发现，空间学习和记忆显着受损时，由Morris水迷宫测试。cKO小鼠在情境和线索恐惧条件反射测试期间也显示冻结时间显著减少，表明恐惧条件反射记忆受到影响。一个显着减少Schaffer侧支长时程增强也记录。形态学上，海马锥体神经元树突分支和棘密度明显减少。原代细胞培养进一步证实了Foxg 1缺失后树突复杂性的改变。我们的研究结果表明，Foxg 1在维持神经可塑性方面起着重要作用，这对高级功能至关重要。
The transcription factor Foxg1 is known to be continuously expressed at a high level in mature neurons in the telencephalon, but little is known about its role in neural plasticity. Mutations in human FOXG1 cause deficiencies in learning and memory and limit social ability, which is defined as FOXG1 syndrome, but its pathogenic mechanism remains unclear. To examine the role of Foxg1 in adults, we crossed Camk2a-Cre(ER) with Foxg1(fl/fl) mice and conditionally disrupted Foxg1 with tamoxifen in mature neurons. We found that spatial learning and memory were significantly impaired when examined by the Morris water maze test. The cKO mice also showed a significant reduction in freezing time during the contextual and cued fear conditioning test, indicating that fear conditioning memory was affected. A remarkable reduction in Schaffer-collateral long-term potentiation was also recorded. Morphologically, the dendritic arborization and spine densities of hippocampal pyramidal neurons were significantly reduced. Primary cell culture further confirmed altered dendritic complexity after Foxg1 deletion. Our results indicated that Foxg1 plays an important role in maintaining the neural plasticity, which is vital to high-grade function.