Inhibition of activated astrocyte ameliorates lipopolysaccharide- induced depressive-like behaviors
Autor: | Jing Ni, Lingyan Zhai, Yun Wang, Liming Xie, Ce Gao, Xiaoxing Yin, Lu Zhao |
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Rok vydání: | 2019 |
Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Lipopolysaccharide Interleukin-1beta Central nervous system Hippocampus Real-Time Polymerase Chain Reaction Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurotrophic factors Internal medicine Glial Fibrillary Acidic Protein medicine Animals Citrates Fluorescent Antibody Technique Indirect Swimming Neuroinflammation Cerebral Cortex Inflammation Depressive Disorder Mice Inbred ICR Tumor Necrosis Factor-alpha Brain-Derived Neurotrophic Factor Antidepressive Agents Tail suspension test 030227 psychiatry Psychiatry and Mental health Clinical Psychology Endocrinology medicine.anatomical_structure chemistry Astrocytes Cytokines 030217 neurology & neurosurgery Behavioural despair test Astrocyte |
Zdroj: | Journal of Affective Disorders. 242:52-59 |
ISSN: | 0165-0327 |
Popis: | 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. |
Databáze: | OpenAIRE |
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