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

Qing-Ren Liu; Cui-Na Shi; Fei Wang; Jian-Hua Tong

doi:10.1016/j.heliyon.2023.e18468

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

Heliyon. 2023 Jul 20;9(8):e18468. doi: 10.1016/j.heliyon.2023.e18468. eCollection 2023 Aug.

Authors

Qing-Ren Liu¹, Cui-Na Shi², Fei Wang², Jian-Hua Tong²

Affiliations

¹ Department of Anesthesiology, Xishan People's Hospital of Wuxi City, Wuxi, 214105, China.
² Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Abstract

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

Keywords: Lipopolysaccharide; Mental disorder; Neuroinflammation; Parvalbumin.