Zhang Qi, Li Tingting, Lin Jia, Zhang Yinglan, Li Fei, Chen Xudong, Wang Xu, Li Qiang
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.
Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
iScience. 2022 Feb 5;25(3):103876. doi: 10.1016/j.isci.2022.103876. eCollection 2022 Mar 18.
The cytoskeletal protein NDE1 plays an important role in chromosome segregation, neural precursor differentiation, and neuronal migration. Clinical studies have shown that NDE1 deficiency is associated with several neuropsychiatric disorders including autism. Here, we generated homologous deficiency zebrafish ( ) to elucidate the cellular molecular mechanisms behind it. exhibit increased neurological apoptotic responses at early infancy, enlarged ventricles, and shrank valvula cerebelli in adult brain tissue. Behavioral analysis revealed that displayed autism-like behavior traits such as increased locomotor activity and repetitive stereotype behaviors and impaired social and kin recognition behaviors. Furthermore, mRNA injection rescued apoptosis in early development, and minocycline treatment rescued impaired social behavior and overactive motor activity by inhibiting inflammatory cytokines. In this study, we revealed that homozygous deletion leads to abnormal neurological development with autism-related behavioral phenotypes and that inflammatory responses in the brain are an important molecular basis behind it.
细胞骨架蛋白NDE1在染色体分离、神经前体分化和神经元迁移中发挥重要作用。临床研究表明，NDE1缺乏与包括自闭症在内的几种神经精神疾病有关。在这里，我们生成了同源缺陷斑马鱼（ ）以阐明其背后的细胞分子机制。 在婴儿早期表现出增加的神经凋亡反应，成年脑组织中的脑室扩大，小脑瓣膜缩小。行为分析表明， 表现出自闭症样行为特征，如运动活动增加和重复刻板行为，以及社会和亲属识别行为受损。此外，mRNA注射挽救了早期发育中的细胞凋亡，米诺环素治疗通过抑制炎性细胞因子挽救了受损的社会行为和过度活跃的运动活动。在本研究中，我们揭示了纯合缺失导致具有自闭症相关行为表型的异常神经发育，并且大脑中的炎症反应是其背后的重要分子基础。
