2. Academic Validation
  3. Nomo1 deficiency causes autism-like behavior in zebrafish

Nomo1 deficiency causes autism-like behavior in zebrafish

  • EMBO Rep. 2024 Jan 22. doi: 10.1038/s44319-023-00036-y.
Qi Zhang # 1,  Fei Li # 1,  Tingting Li 1,  Jia Lin 1,  Jing Jian 1,  Yinglan Zhang 1,  Xudong Chen 1,  Ting Liu 1,  Shenglan Gou 1,  Yawen Zhang 1,  Xiuyun Liu 1,  Yongxia Ji 1,  Xu Wang 2 3 4,  Qiang Li 5
Affiliations

Affiliations

  • 1 Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, 210013, Shanghai, China.
  • 2 Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, 200032, Shanghai, China.
  • 3 Shanghai Pancreatic Cancer Institute, Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 200032, Shanghai, China.
  • 4 Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, 200032, Shanghai, China.
  • 5 Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, NHC Key Laboratory of Neonatal Diseases, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, 210013, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 38253686 DOI: 10.1038/s44319-023-00036-y
Abstract

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of Apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Keywords

Inflammatory Response; Melatonin; Neuropsychiatric Disorders; Nomo1; Serotonin.

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