2. Academic Validation
  3. The role of reelin in the pathological mechanism of depression from clinical to rodents

The role of reelin in the pathological mechanism of depression from clinical to rodents

  • Psychiatry Res. 2022 Nov;317:114838. doi: 10.1016/j.psychres.2022.114838.
Kangyu Jin 1,  Shiyi Zhang 1,  Chaonan Jiang 1,  Ripeng Liu 2,  Bing Chen 1,  Haoyang Zhao 1,  Qin Zhang 2,  Zhe Shen 3,  Pengfeng Xu 1,  Xiaohan Hu 1,  Jianping Jiao 1,  Jing Lu 4,  Manli Huang 5
Affiliations

Affiliations

  • 1 Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; The Key Laboratory of Mental Disorder Management in Zhejiang Province, Hangzhou 310003, China.
  • 2 College of First Clinical College, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou 310053, China.
  • 3 Department of Child Psychology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
  • 4 Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; The Key Laboratory of Mental Disorder Management in Zhejiang Province, Hangzhou 310003, China. Electronic address: [email protected].
  • 5 Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; The Key Laboratory of Mental Disorder Management in Zhejiang Province, Hangzhou 310003, China. Electronic address: [email protected].
PMID: 36103758 DOI: 10.1016/j.psychres.2022.114838
Abstract

Major depressive disorder (MDD) is a devastating mental illness and the leading cause of disability worldwide. Previous studies have suggested that synaptic plasticity in the hippocampus plays an important role in depression pathogenesis. Reelin is expressed mainly in the frontal lobe and hippocampus, and is closely associated with neurodevelopment and synaptic plasticity. However, few studies have investigated its role in MDD combining clinical trials and animal experiments. We show that in a clinical trial, plasma reelin levels decreased in patients with first-episode drug-naïve MDD and increased after treatment; further, plasma reelin levels allowed to distinguish drug-naïve patients with first-episode MDD from healthy individuals. In rats, chronic mild and unpredictable stress led to a decrease in both reelin mRNA and protein levels in the hippocampus, which could be reversed by vortioxetine. Subsequent experiments confirmed that the reelin-ApoER2-NR2A /NR2B pathway regulates hippocampal synaptic plasticity and may be involved in depression or antidepressant responses. Our work contributes to a deeper understanding of MDD pathogenesis and provides new evidence that reelin should be considered a potential therapeutic target for MDD.

Keywords

Major depressive disorder; NMDAR; Reelin; Synaptic plasticity; Vortioxetine.

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