期刊
JOURNAL OF AFFECTIVE DISORDERS
卷 330, 期 -, 页码 83-93出版社
ELSEVIER
DOI: 10.1016/j.jad.2023.02.105
关键词
Depressive; Microglia; Neuro-inflammation; Osteopontin
Neuroinflammation is important in the development of major depressive disorder, and osteopontin (OPN) plays a key role in neuroinflammation. This study demonstrates the crucial role of OPN in lipopolysaccharide-induced depressive-like behavior.
Introduction: Neuroinflammation plays an important role in the development of major depressive disorder (MDD). Osteopontin (OPN) is one of the key molecules involved in neuroinflammation. We demonstrate here for the first time a key role of OPN in lipopolysaccharide (LPS)-induced depressive-like behavioral syndrome.Methods: Systemic administration of LPS (5 mg/kg) mimics distinct depressive-like behavior, which could significantly upregulate OPN expression in microglia/macrophage in the hippocampus. The neurobehavioral assessments, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), Western blot, immunofluorescent staining, flow cytometry cell staining and Golgi staining were performed.Results: Similar to fluoxetine treatment (the positive control), OPN knockdown with shRNA lentivirus markedly reversed LPS-induced depressive-like behavior. Moreover, knockdown of OPN suppressed LPS-induced proinflammatory cytokine expression, microglial activation, dendritic spines loss, as well as unregulated PSD-95 and BDNF in the hippocampus.Conclusion: We demonstrated that targeting OPN expression in microglia/macrophage might help to rescue LPSinduced depressive-like behavior. The underlying mechanism may relate to the modulation of neuroinflammation, BDNF signaling and synaptic structural complexity.
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