Dataset Information

Proteomic and Behavioral Study of the Anxiolytic Effects of GABA in a Chronic Restraint Stress-Induced Anxiety Model

ABSTRACT: This study aimed to investigate the anxiolytic effects of GABA administration and its underlying molecular mechanisms in a chronic restraint stress (CRS)-induced anxiety model in C57BL/6J mice. CRS mice were established by placing the animals in well-ventilated 50 ml centrifuge tubes for 2 hours daily over 14 consecutive days, while control mice were housed under standard conditions. Behavioral assessments, including the elevated plus maze (EPM) test and open field test (OFT), were performed on days 15 and 16, respectively. GABA was administered intragastrically at various doses throughout the experiment, and prefrontal cortex (PFC) and hippocampal tissues were harvested on day 17 for further proteomic and biochemical analyses. Behavioral results demonstrated that GABA treatment exerted dose-dependent anxiolytic effects, as evidenced by increased time and entries in the open arms in the EPM and increased time and distance spent in the center area in the OFT. Furthermore, GABA treatment significantly elevated reduced GABA levels in the PFC. To elucidate the molecular mechanisms of GABA’s anxiolytic effects, a 4D-label-free quantitative proteomics approach was employed. Principal component analysis (PCA) and differential protein analyses revealed that CRS induced substantial proteomic alterations in the hippocampus, while GABA treatment partially reversed these changes. Functional clustering (Mfuzz) and gene ontology (GO) enrichment analysis identified critical pathways involved in the “humoral immune response,” “complement activation,” and “acute inflammatory response.” Key proteins such as C3, Cfh, C4b, and Cfi were found to overlap across these pathways, highlighting their involvement in CRS-induced neuroimmune dysfunction and GABA-mediated rescue effects. This integrated analysis provides valuable insights into the behavioral and neuroimmune mechanisms through which GABA alleviates anxiety-like behaviors, shedding light on its potential as a therapeutic agent for stress-related disorders.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Jiyi Xu

LAB HEAD: JING DU

PROVIDER: PXD059153 | Pride | 2025-05-07

REPOSITORIES: Pride

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			Action	DRS
	XA02828DA.d.zip	Other
	txt.zip	Other

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Publications

Long-term GABA supplementation mitigates anxiety by modulating complement and neuroinflammatory pathways.

Xu Jiyi J Ge Ziyu Z Wang Han H Zhang Chenhui C Xu Jinjie J Li Ying Y Yang Xiangyun X Zhang Ling L Li Zhanjiang Z Liu Zhe Z Wang Gang G Du Jing J

NPJ science of food 20250424 1

Anxiety disorders are among the most prevalent mental health conditions, often linked with neuroinflammation and imbalances in neurotransmitter systems. This study examined the anxiolytic effects of oral GABA in chronic restraint stress (CRS) mice. Mice were divided into control, CRS, and two GABA-treated groups (10 mg/kg, 20 mg/kg). After 14 days of administration, anxiety-like behaviors were assessed using elevated-plus maze and open-field tests. GABA levels in the prefrontal cortex were quant ...[more]

PMID: 40274802

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