GABA modulate NF-κB/NLRP3 pathways in electroacupuncture prevention of depression in CUMS rats.

BACKGROUND

Our previous research has demonstrated that electroacupuncture (EA) has the potential to mitigate depression-like symptoms resulting from chronic stress. However, further investigation is required to fully understand the underlying mechanisms. The regulatory role of γ-aminobutyric acid type B (GABA) in synaptic plasticity and the involvement of NF-κB/NLRP3-mediated inflammation in the lateral habenula nucleus (LHb) are key factors in the development of depression. This study sought to investigate the potential of EA in mitigating depression-like symptoms induced by chronic stress through mechanisms such as enhancing GABA levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation.

METHODS

Sprague-Dawley rats were exposed to chronic unpredictable mild stress (CUMS) in order to create a model of depression. Subsequently, the weight and behavioral assessments of all rats were monitored, and samples of the lateral habenula and serum were collected. The protein expression levels were analyzed using western blotting. The 5-hydroxytryptophan (5-HT), Dopamine (DA), and Norepinephrine (NE) in the LHb and serum were measured using ELISA. The alterations in GABA and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining.

RESULTS

EA upregulated the expression of GABA in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABA attenuated the antidepressant effects of EA in CUMS-exposed rats. Furthermore, EA enhanced synaptic plasticity in the LHb of CUMS-exposed rats and mitigated NF-κB/NLRP3-mediated inflammatory responses, with these effects potentially being reversed by GABA inhibition.

CONCLUSION

Through the promotion of GABA levels, regulation of synaptic plasticity within the LHb, and inhibition of NF-κB/NLRP3-mediated neuroinflammation in the same region, electroacupuncture at Shangxing and Fengfu acupoints demonstrates efficacy in mitigating depression-like behaviors induced by CUMS.