Prelimbic cortical stimulation ameliorates inflammation-induced social behavioural deficits and depressive-like behaviours

Abstract

Deep brain stimulation (DBS) is a promising neuromodulation therapy for treatment-resistant depression. Previous studies have reported the comorbidity of neuroinflammation and depression, but the underlying mechanisms of the stimulation-induced antidepressive effects on neuroinflammatory elements remain largely unknown. This study aimed to investigate the anti-neuroinflammatory effects of DBS of the prelimbic cortex (PrL-DBS) in rat models of depression. Rats received either electric stimulation or sham stimulation of the prelimbic cortex and then underwent 3 weeks of a chronic unpredictable stress (CUS) paradigm. Rats were subjected to 1 hour of high-frequency stimulation (100 Hz) at 200 µA amplitude prior to testing for social interaction and depressive-like behaviours. Their brains were processed to further elucidate the anti-neuroinflammatory-related mechanisms of DBS-induced antidepressant activity. A further investigation in another animal depression model using a combined CUS and lipopolysaccharide (LPS) treatment paradigm was conducted to examine the anti-neuroinflammatory-dependent and/or -independent mechanisms of DBS-induced antidepressant activity. In both CUS- and CUS plus LPS-induced depression models, we observed increased social interaction and decreased forced swim immobility time in animals with DBS of the prelimbic cortex compared to sham stimulation. Interestingly, the gene expression study found significant neuroinflammatory-related changes after DBS. These results were further supported by the morphological analysis of microglial expression within the prefrontal cortical areas. The study findings demonstrated that PrL-DBS in rats enhanced social interaction and antidepressive-like behaviours. The results also showed that the DBS-induced changes in the neuroinflammatory environment were mediated by both neuroinflammatory-dependent and -independent mechanisms.