Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior

iScience

卷:25

Qiang Li¹  Xu Wang²  Fei Li³  Jia Lin³  Yinglan Zhang³  Xudong Chen³  Tingting Li³  Qi Zhang³ 

[1] Shanghai Pancreatic Cancer Institute, Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China;

[2] Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China;

[3] 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;

关键词: Biological sciences;    Molecular neuroscience;    Developmental neuroscience;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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 nde1 homologous deficiency zebrafish (nde1−/−) to elucidate the cellular molecular mechanisms behind it. nde1−/− exhibit increased neurological apoptotic responses at early infancy, enlarged ventricles, and shrank valvula cerebelli in adult brain tissue. Behavioral analysis revealed that nde1−/− displayed autism-like behavior traits such as increased locomotor activity and repetitive stereotype behaviors and impaired social and kin recognition behaviors. Furthermore, nde1 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 nde1 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.

【 授权许可】

Unknown