Yun Wang1, Jing Ni1, Lingyan Zhai1, Ce Gao1, Liming Xie1, Lu Zhao1, Xiaoxing Yin2. 1. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Jiangsu, China. 2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Jiangsu, China. Electronic address: yinxx@xzhmu.edu.cn.
Abstract
BACKGROUND: Numerous studies indicate that inflammation plays important roles in the development of depression. Astrocytes are crucial regulators of immune response in the central nervous system, and strongly activated by pro-inflammatory cytokines. We hypothesized that inhibition of activated astrocytes contributed to ameliorate depressive-like symptoms. METHODS: This study evaluated the antidepressant-like effect of inhibition of activated astrocytes, by a well-established astrocyte inactivator fluorocitrate (FC), on a lipopolysaccharide (LPS)-induced model of depression. Forced swim test (FST), tail suspension test (TST) and sucrose preference test were used to assess depressive-like behaviors. The expression of fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neuroinflammation were determined in the hippocampus and cortex. RESULTS: The results demonstrated that LPS increased immobility time in the TST and FST, reduced sucrose preference as well. LPS also enhanced the expression of IL-1β, TNF-α, iNOS and GFAP, accompanying with decreased expression of BDNF in the hippocampus and cortex. Inhibition of activated astrocytes by FC significantly prevented LPS- induced alteration in the FST, TST and sucrose preference test. Moreover, in the hippocampus and cortex, inhibition of activated astrocytes by FC significantly attenuated increases of neuroinflammation and GFAP whereas reversed decrease of BDNF in LPS- challenged depression. CONCLUSIONS: Taken together, the results suggest that inhibition of activated astrocytes ameliorates LPS-induced depressive-like behavior, providing the first evidence that inhibition of activated astrocytes might represent a novel therapeutic target for depression.
BACKGROUND: Numerous studies indicate that inflammation plays important roles in the development of depression. Astrocytes are crucial regulators of immune response in the central nervous system, and strongly activated by pro-inflammatory cytokines. We hypothesized that inhibition of activated astrocytes contributed to ameliorate depressive-like symptoms. METHODS: This study evaluated the antidepressant-like effect of inhibition of activated astrocytes, by a well-established astrocyte inactivator fluorocitrate (FC), on a lipopolysaccharide (LPS)-induced model of depression. Forced swim test (FST), tail suspension test (TST) and sucrose preference test were used to assess depressive-like behaviors. The expression of fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neuroinflammation were determined in the hippocampus and cortex. RESULTS: The results demonstrated that LPS increased immobility time in the TST and FST, reduced sucrose preference as well. LPS also enhanced the expression of IL-1β, TNF-α, iNOS and GFAP, accompanying with decreased expression of BDNF in the hippocampus and cortex. Inhibition of activated astrocytes by FC significantly prevented LPS- induced alteration in the FST, TST and sucrose preference test. Moreover, in the hippocampus and cortex, inhibition of activated astrocytes by FC significantly attenuated increases of neuroinflammation and GFAP whereas reversed decrease of BDNF in LPS- challenged depression. CONCLUSIONS: Taken together, the results suggest that inhibition of activated astrocytes ameliorates LPS-induced depressive-like behavior, providing the first evidence that inhibition of activated astrocytes might represent a novel therapeutic target for depression.