Journal
EXPERIMENTAL NEUROLOGY
Volume 365, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2023.114426
Keywords
Depression; Bergapten; Microglia; Neuroinflammation; Cyclooxygenase 2
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Major depressive disorder (MDD) is a common psychiatric disorder that severely affects human life and health. The study found that bergapten (BG) can alleviate depression-like behavior induced by inflammation and protect against microglial activation and neuroinflammation. Thus, BG may serve as a new candidate drug for depression treatment.
Major depressive disorder (MDD) is a common psychiatric disorder that severely affects human life and health. However, the pathological mechanism of MDD is unclear, and effective treatment strategies are urgently needed. Microglia-mediated neuroinflammation is closely associated with the pathophysiology of depression. Bergapten (BG) is a natural pharmaceutical monomer with anti-inflammatory effects; however, its role in neuroinflammation and depression remains unclear. In this study, we employed a lipopolysaccharide (LPS) injectioninduced acute depression mouse model, and found that treatment with BG significantly alleviated LPS-induced depression-like behavior in mice. BG administration largely decreased the increase in microglial numbers and rescued the microglial morphological changes induced by LPS injection. Furthermore, transcriptomic changes revealed a protective role of BG in the hippocampus of mice. Mechanistically, we found that BG directly inhibited cyclooxygenase 2 (COX2) activity, and suppressed nuclear factor-xB (NF-xB) and mitogen-activated protein kinase (MAPK) signaling pathways in microglia. Together, these results highlight the important role of BG in microglial activation, neuroinflammation, and depression-like behavior, thus providing a new candidate drug for depression treatment.
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