Conditional deletion of MAD2B in forebrain neurons enhances hippocampus-dependent learning and memory in mice.
Conditional deletion of MAD2B in forebrain neurons enhances hippocampus-dependent learning and memory in mice.
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DOI：
10.3389/fncel.2022.956029
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
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有丝分裂阻滞缺陷2样蛋白2 （MAD2B）不仅是一种DNA损伤修复剂，也是一种细胞周期调节剂，广泛表达于海马和大脑皮层。然而，MAD2B在海马和大脑皮层神经元中的功能尚不清楚。在本研究中，我们通过Cre/loxP重组酶系统，将MAD2Bflox/flox与钙/钙调素依赖性蛋白激酶II α (Camk2a)-Cre小鼠杂交，有条件地敲除前脑锥体神经元中的MAD2B。首先，RNA测序显示WT和MAD2B cKO小鼠海马和大脑皮层中差异表达的基因与学习记忆有关。Morris水迷宫实验、新物体识别实验、情境恐惧条件反射实验等行为测试结果表明，MAD2B cKO小鼠的学习记忆能力得到改善。此外，条件敲除MAD2B增加了神经元数量，但不影响海马CA1和大脑皮层的胶质细胞数量。同时，MAD2B cKO小鼠齿状回（DG）双皮质素阳性（DCX+）细胞数量增加。此外，高尔基染色显示，MAD2B cKO小鼠比WT小鼠具有更多的蘑菇状和长状棘。透射电镜（TEM）显示，MAD2B cKO小鼠CA1中脊柱突触增加，轴突触减少。综上所述，我们的研究结果表明MAD2B在调节学习和记忆中起着至关重要的作用。
Mitotic arrest deficient 2-like protein 2 (MAD2B) is not only a DNA damage repair agent but also a cell cycle regulator that is widely expressed in the hippocampus and the cerebral cortex. However, the functions of MAD2B in hippocampal and cerebral cortical neurons are poorly understood. In this study, we crossed MAD2Bflox/flox and calcium/calmodulin-dependent protein kinase II alpha (Camk2a)-Cre mice to conditionally knock out MAD2B in the forebrain pyramidal neurons by the Cre/loxP recombinase system. First, RNA sequencing suggested that the differentially expressed genes in the hippocampus and the cerebral cortex between the WT and the MAD2B cKO mice were related to learning and memory. Then, the results of behavioral tests, including the Morris water maze test, the novel object recognition test, and the contextual fear conditioning experiment, suggested that the learning and memory abilities of the MAD2B cKO mice had improved. Moreover, conditional knockout of MAD2B increased the number of neurons without affecting the number of glial cells in the hippocampal CA1 and the cerebral cortex. At the same time, the number of doublecortin-positive (DCX+) cells was increased in the dentate gyrus (DG) of the MAD2B cKO mice. In addition, as shown by Golgi staining, the MAD2B cKO mice had more mushroom-like and long-like spines than the WT mice. Transmission electron microscopy (TEM) revealed that spine synapses increased and shaft synapses decreased in the CA1 of the MAD2B cKO mice. Taken together, our findings indicated that MAD2B plays an essential role in regulating learning and memory.
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影响因子：
16.2
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