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

Qi Zhang; Tingting Li; Jia Lin; Yinglan Zhang; Fei Li; Xudong Chen; Xu Wang; Qiang Li

iScience (Mar 2022)

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

Qi Zhang,
Tingting Li,
Jia Lin,
Yinglan Zhang,
Fei Li,
Xudong Chen,
Xu Wang,
Qiang Li

Affiliations

Qi Zhang: 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
Tingting Li: 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
Jia Lin: 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
Yinglan Zhang: 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
Fei Li: 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
Xudong Chen: 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
Xu Wang: Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
Qiang Li: 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; Corresponding author

Journal volume & issue: Vol. 25, no. 3
p. 103876

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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