A New Perspective on Ameliorating Depression-Like Behaviors: Suppressing Neuroinflammation by Upregulating PGC-1α

Inflammation plays an important role in depression pathology, making it a promising target for ameliorating depression-like behaviors. The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a transcriptional coactivator being able to constrain inflammatory events through NF-kappa B signaling. However, the role of PGC-1 alpha in depression is not yet clear. This study was designed to investigate the role of PGC-1 alpha in depression and explore the underlying mechanisms. Mice modeled with chronic unpredictable mild stimulation (CUMS) were explored for the relationship between depression-like behaviors and PGC-1 alpha. Baicalin was used to evaluate the effect regulating PGC-1 alpha. Furthermore, the anti-neuroinflammatory effect of baicalin was investigated both in BV2-SH-SY5Y co-culture system and in mice by LPS challenge. The role of PGC-1 alpha in neuroinflammation was explored in cell co-culture systems under gene silencing conditions targeting NF-kappa B signaling. We found that the expression of PGC-1 alpha was inhibited in the hippocampus of mice exposed to CUMS or LPS, while baicalin could increase the expression of PGC-1 alpha and alleviate the depression-like behaviors. Furthermore, baicalin attenuated neuroinflammation in the hippocampus of mice and BV2-SH-SY5Y co-culture system by LPS challenge via regulating NF-kappa B signaling; however, knockdown of the PGC-1 alpha could reverse the effect of baicalin on neuroinflammation and NF-kappa B signaling. Our results revealed a vital role for PGC-1 alpha in attenuating neuroinflammation in depression, indicating that PGC-1 alpha might be a therapeutic target for depression.

Automated summary

In this study, the researchers investigated the role of PGC-1 alpha in depression and explored its underlying mechanisms. The results showed that PGC-1 alpha expression was inhibited in mice exposed to CUMS or LPS, while baicalin could increase its expression and alleviate depression-like behaviors. Baicalin also attenuated neuroinflammation in mice through regulating NF-kappa B signaling, suggesting that PGC-1 alpha might be a therapeutic target for depression.