Prelimbic cortical stimulation ameliorates the neuroinflammatory-induced depressive-like and social behavioral deficits in rat models

Abstract

Deep brain stimulation (DBS) is a promising neuromodulation therapy for treatmentresistant depression. Although previous studies have reported the comorbidity of neuroinflammation and depression, the underlying mechanisms of stimulationinduced antidepressive effects on neuroinflammatory elements remain largely unknown. In this study, we aimed to investigate the antineuroinflammatory role of DBS of the prelimbic cortex in rat models of depression. Rats received either stimulating or sham electrodes in the prelimbic cortex and underwent through a 3weeks Chronic Unpredictable Stress (CUS) paradigm. We performed 1hour of highfrequency stimulation (100 Hz) at 200 μA amplitude prior to testing for social interaction and depressivelike behaviors. The brains were processed for immunohistochemical/biochemical investigation to further elucidate the antineuroinflammatoryrelated mechanisms of DBS-induced antidepressants. Additionally, a followup study was performed to examine the antineuroinflammatorydependent and/or independent mechanisms of DBS-induced antidepressants using animal models with a combined CUS and lipopolysaccharide-induction paradigm. In both the CUS and CUS-combined with lipopolysaccharide-induced depression models, we observed an increase in social interaction and a decrease in forced swim immobility time in animals with DBS of the prelimbic cortex as compared to sham. Interestingly, our gene expression study found significant changes in the neuroinflammatory environment postDBS. These results were further supported by morphological analysis of microglial expression within the prefrontal cortical areas. These findings demonstrate that DBS of the prelimbic cortex enhances social interaction and antidepressant-like behaviors. Our results show that the DBS-induced changes in the neuroinflammatory environment were mediated by both the neuroinflammatory-dependent and independent mechanisms in animal models.