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

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Anxiety disorders are common mental health issues associated with neuroinflammation and neurotransmitter imbalances.
• Chronic restraint stress (CRS) is a model used to study anxiety-related conditions.

Purpose of the Study:

• To investigate the anxiolytic effects of oral gamma-aminobutyric acid (GABA) in a mouse model of chronic restraint stress (CRS).
• To explore the impact of GABA on neurotransmitter levels, neuroinflammation, and protein expression in the brain.

Main Methods:

• Mice were subjected to CRS and treated with varying doses of oral GABA.
• Anxiety-like behaviors were assessed using the elevated-plus maze and open-field tests.
• GABA levels, anti-inflammatory cytokines (IL-10, TGF-β1), and hippocampal proteins involved in complement pathways were quantified.

Main Results:

• GABA administration significantly reduced anxiety-like behaviors in CRS mice.
• Oral GABA increased GABA levels in the prefrontal cortex and elevated anti-inflammatory cytokines IL-10 and TGF-β1.
• Proteomic analysis revealed that GABA reversed stress-induced dysregulation of complement proteins (C3, C4b, Cfh, Cfi).

Conclusions:

• Oral GABA demonstrates significant anxiolytic effects in a mouse model of chronic stress.
• GABA's therapeutic potential may stem from its ability to restore immune homeostasis and modulate complement system activation in the brain.
• These findings highlight GABA as a promising therapeutic agent for anxiety disorders.