BNST^GABA neurons regulate autophagy to alleviate depression with gastric dysfunction symptoms

Gastric dysfunction is very common in depressed patients, and the coupling mechanism between the brain and the stomach is a key point in its occurrence. Electroacupuncture (EA) can act on both 'form' (i.e., the physical level) and 'spirit' (i.e., the mental-emotional level) in the treatment of negative emotions and gastrointestinal co-morbidities, realising the therapeutic effect of'form-spirit co-medication'. The neurological mechanism is not clear.We developed a chronic unpredictable stress (CUMS) model, and gastric electrophysiological and behavioural results suggest that EA can alleviate depressive symptoms and improve gastric dysfunction accompanying depression. We found that the CUMS model inhibits GABAergic neurons in the bed nucleus of the stria terminalis (BNST), whereas BNST^GABA neurons are de-suppressed after EA intervention. Chemical activation of BNST^GABA neurons eliminated CUMS-induced depressive symptoms and gastric dysfunction with effects similar to EA treatment. In addition, transcriptomics data showed that excessive autophagy was present in the gastric tissues of CUMS model mice, which was alleviated by EA, and it was verified by Western Blot that EA may ameliorate depression-induced gastric dysfunction by modulating BNST^GABA neurons, which effectively inhibited excessive autophagy in the cells of gastric tissues. Thus, our study describes a neural mechanism that regulates autophagy in gastric cells via BNST^GABA neurons, thereby alleviating gastric dysfunction in depression, and provides a theoretical basis for electroacupuncture in the treatment of mood disorders with comorbid somatic symptoms.