时间：2022年6月9日（星期四）8:30-10:30

会议号：腾讯会议180 406 819

主办：华中农业大学、湖北洪山实验室

承办：生物医学与健康学院

报告人1：陈姣 8:30-9:30

题目：原癌基因Mycn在成年神经发生和胶质发生中的作用

Function of oncogene Mycn in adult neurogenesis and oligodendrogenesis

摘要：人类原癌基因MYCN 主要在脑瘤和其他许多肿瘤中大量扩增。人源MYCN 和鼠源Mycn 基因在胚胎脑发育中具有重要作用，但是Mycn在健康成年中枢系统中的作用并不清楚。本研究通过使用Mycn-eGFP 小鼠和qRT-PCR，发现Mycn 在成年小鼠侧脑室（SVZ）、亚颗粒区（SGZ）、嗅球（OB）、亚胼胝体（SCZ）和胼胝体（CC）等特定脑区中有表达。通过免疫组化的方法，发现许多表达Mycn 的细胞同时表达神经瘤标记物DCX 和细胞增殖标记物Ki67。通过使用Dcx-creER 和Mki67-creER 两种鼠系，可分别标记Mycn 基因敲除后Dcx 和Mki67 阳性细胞。发现Mycn 基因敲除后的神经瘤和增殖细胞在以上5 个脑区的增殖能力明显降低。同时发现SGZ 区中缺乏Mycn 基因的神经瘤细胞比野生型成熟更早，SVZ、SGZ、OB、SCZ、CC 区中缺乏Mycn 基因的增殖细胞比野生型更易存活。因此，本研究表明，Mycn 基因不仅诱发中枢系统肿瘤，而且它在健康成年大脑的神经发生和胶质发生中也具有重要作用。

Human MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their function in adult healthy nerve system is completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adultmice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC) we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in nervous system, oncogene Mycn has crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.

报告人2：姚玉霄 9:30-10:30

题目：脯氨酸代谢酶Prodh调控神经元形态功能从而影响精神分裂症相关行为的机制研究

The mechanism of Prodh in proline metabolism modulates neuronal morphology and function following schizophrenia-like behavior

摘要：精神分裂症是一种严重的慢性精神障碍，典型发病于青少年晚期或者成年早期。69%的精神分裂症患者病痛伴随一生且得不到有效的治疗。目前精神分裂症的发病原因和机制尚不明确。临床研究表明，脯氨酸代谢酶Prodh的突变与精神分裂症发生存在一定的相关性。但Prodh及脯氨酸代谢在精神分裂症中是否起着关键性作用并不清楚。脯氨酸是人体的一种非必需氨基酸，参与细胞氧化还原、凋亡以及分化等重要过程。本研究利用小鼠模型发现，敲低小鼠海马区Prodh导致小鼠出现精神分裂症样行为。进一步在该敲低模型的海马区中，其神经元形态发生改变。体外原代神经元的培养显示，敲低Prodh导致神经元树突长度以及神经元相关标记物发生改变。这部分研究工作提示脯氨酸及其重要的代谢酶通过改变神经元形态与功能从而影响动物行为。该部分的研究为精神分裂症的发病机制提供新的思路。

Schizophrenia is a chronic mental disorder that typically develops in late adolescence or early adulthood. 69% of schizophrenia patients suffer from life-long pain without effective treatment. The etiology and mechanism of schizophrenia are still unclear. Clinical studies have shown that several polymorphisms of Prodh in proline metabolism are significantly associated with schizophrenia susceptibility. However, it is not clear whether Prodh and proline metabolism play a key role in schizophrenia. Proline is a non-essential amino acid which is involved in cellular redox, apoptosis and differentiation processes. By using mouse model, it showed that knockdown of Prodh in mouse hippocampus led to schizophrenia-like behavior. Moreover, the morphology of neurons in mouse hippocampus was abnormal. In vitro, knockdown of Prodh increased the length of dendrites and changed several neuron synapse markers’ expressions. This study indicates that proline metabolism and its key enzyme Prodh changes animals’ behavior through influence the morphology and function of neurons. This study will provide new ideas for the mechanism of schizophrenia.