Neuroinflammation-induced parvalbumin interneuron and oscillation deficits might contribute to neurobehavioral abnormities in a two-hit model of depression

Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, present study aimed to evaluate effects of two-hit model depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, whether chronic fluoxetine treatment can reverse these abnormalities. Male mice were submitted lipopolysaccharide (LPS) injection, followed by modified unpredictable stress (CUS) protocol. In our study, we showed exposed LPS CUS exhibited reduced body weight, anhedonic-like as well cognitive anxiety symptoms. These behavioral alternations related enhanced neuroinflammation, reflected significantly increased IL-1β IL-6 levels microglia activation in prefrontal cortex (PFC). addition, displayed decreased PV expression disturbance theta gamma oscillations PFC. However, reversed most conclusion, suggests neuroinflammation-induced interneuron deficits might contribute neurobehavioral abnormalities depression.