Cited by 13Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

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

Jin, Kangyu, Zhang, Shiyi, Jiang, Chaonan, Liu, Ripeng, Chen, Bing, Zhao, Haoyang, Zhang, Qin, Shen, Zhe +5 more·2022·Psychiatry Research

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.

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Crossref · 10.1016/j.psychres.2022.114838

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Authors
Jin, K., Zhang, S., Jiang, C., Liu, R., Chen, B., Zhao, H., Zhang, Q., Shen, Z., Xu, P., Hu, X., Jiao, J., Lu, J., & Huang, M.
Affiliations
  • First Affiliated Hospital Zhejiang University (CN)
  • Zhejiang Chinese Medical University (CN)
  • Children's Hospital of Zhejiang University (CN)
Corresponding author
Huang, Manli
Venue
Psychiatry Research
Publisher
Elsevier BV
Published
2022-11
Volume
317
Pages
114838
ISSN
0165-1781 (ISSN-L)
OpenAlex
W4294708709
Cited by
13
References
59
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 2
FWCI
1.65
Type
journal article
Language
en
Open access
closed
Locations
  • Psychiatry Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81801340)
  • Medical Science and Technology Project of Zhejiang Province (2022RC024)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
reelin, major depressive disorder, hippocampal synaptic plasticity, vortioxetine, ApoER2, antidepressant response, first-episode drug-naive depression, biomarkers, therapeutic target
MeSH terms
Reelin Protein, Animals, Clinical Trials as Topic, Depression, Depressive Disorder, Major, Major Depressive Disorder, Hippocampus, Nerve Tissue Proteins, Rodentia, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Rats

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