Ke Cheng, Chong Chen, Qinji Zhou, Xiangyu Chen, Peng Xie
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引用次数: 0
Abstract
Introduction
Major depressive disorder (MDD) is a severe neuropsychiatric disease that is accompanied by hippocampal dysfunction. Currently, the complex neuronal types and molecules involved in the various hippocampal subfields in patients with depression remain unclear.
Objectives
We focused on the role of hippocampal excitatory amino acid transporter 2 (EAAT2) in chronic stress.
Methods
We studied two chronic stress models, the chronic unpredictable mild stress (CUMS) and the chronic social defeat stress (CSDS) models, and performed pharmacological inhibition, genetic manipulations to examine overexpression of neuron-specific solute carrier family 1 member 2 (SLC1A2), the gene encoding EAAT2, in the dorsal CA3 and conditional Slc1a2 knockout in CA3, whole-cell recording, and behavioral tests.
Results
Our results indicated that decreased EAAT2 expression and specific inhibition were associated with depression-like behavior and enhanced CA3 pyramidal neuron activity. In addition, neuron-specific EAAT2 overexpression in the CA3 yielded antidepressant-like effects and inhibited CA3 pyramidal neuron hyperactivity, whereas conditional CA3 EAAT2 knockout showed opposite effects at both behavioral and functional levels. We also found that the single-nucleotide polymorphism, rs77619780, in the SLCA1A2 gene was associated with lower MDD risk.
Conclusion
Our findings revealed that EAAT2 deficit in the CA3 induces depression-like behavior, which offers novel insight into MDD pathophysiology.
期刊介绍:
Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences.
The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.