Aquaporin‐4 Knockout Exacerbates Corticosterone‐Induced Depression by Inhibiting Astrocyte Function and Hippocampal Neurogenesis
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Summary: Aims: The predominant expression of aquaporin‐4 (AQP 4) in the brain implies that this water channel may be involved in a range of brain disorders. This study was designed to investigate the role of AQP 4 in the pathogenesis of depression, and related possible biological mechanism. Methods and Results: Wild‐type (AQP 4+/+) and AQP 4 knockout (AQP 4−/−) mice were given daily subcutaneous injections of corticosterone (20 mg/kg) for consecutive 21 days. Forced swimming test (FST) and tail suspension test (TST) showed longer immobility times in corticosterone‐treated AQP 4−/− genotype, indicating AQP 4 knockout exacerbated depressive‐like behaviors in mice. Using immunohistological staining, western blot, and enzyme‐linked immunosorbent assay (ELISA), we found a significant loss of astrocytes, aggravated downregulation of excitatory amino acid transporter 2 (EAAT 2), synapsin‐1, and glial cell line‐derived neurotrophic factor (GDNF) in the hippocampus of AQP 4−/− mice. Moreover, even less hippocampal neurogenesis was identified in corticosterone‐treated AQP 4−/− mice in vivo and hippocampus‐derived adult neural stem cells (ANSC s) in vitro. Conclusions: The present findings suggest AQP 4 involves the pathogenesis of depression by modulating astrocytic function and adult neurogenesis, highlighting a novel profile of AQP 4 as a potential target for the treatment for depression.
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K+-buffering capacity and presumably synaptic transmission are impaired in mice lacking AQP4, and impairment of these processes is associated with depressive-like behaviors.
“In addition, the K + -buffering capacity and presumably synaptic transmission are impaired in mice lacking AQP4, and impairment of these processes is associated with depressive-like behaviors. 171”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [171]
The Discussion (page not specified) links reduced hippocampal synapsin-1 in corticosterone-treated AQP4-knockout mice to possible presynaptic impairment and exacerbated depressive-like behavior. The Introduction mentions attenuated ion homeostasis after AQP4 loss, but the paper does not establish impaired K+-buffering capacity or link that specific process to depressive-like behavior. (LLM, conf=0.87)
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- Authors
- Kong, H., Zeng, X., Fan, Y., Yuan, S., Ge, S., Xie, W., Wang, H., & Hu, G.
- Affiliations
- Jiangsu Province Hospital (CN)
- Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing China
- Nanjing Medical University (CN)
- Jiangsu Key Laboratory of Neurodegeneration Department of Pharmacology Nanjing Medical University Nanjing China
- Department of Neurology The First Affiliated Hospital of Nanjing Medical University Nanjing China
- Corresponding author
- Kong, Hui
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2014-01-15
- Volume
- 20
- Issue
- 5
- Pages
- 391-402
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6493035
- OpenAlex
- W2091166955
- Cited by
- 72
- References
- 60
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 4 · 2017: 3 · 2016: 9 · 2015: 7 · 2014: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81001428, 81000119, 81173032, 81001427, 81070743)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- aquaporin-4, depression, corticosterone, astrocytes, hippocampal neurogenesis, adult neurogenesis, GLT-1, synapsin-1, glial cell line-derived neurotrophic factor, adult neural stem cells, aquaporins, AQP4 knockout mice, depression-like behavior
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Corticosterone, Depressive Disorder, Disease Models, Animal, Hippocampus, Male, Mice, Inbred Strains, Down-Regulation, Synapsins, Cell Death, Mice, Knockout, Excitatory Amino Acid Transporter 2, Glial Cell Line-Derived Neurotrophic Factor, Aquaporin 4, Neurogenesis
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