Abstract
BackgroundRecently, depression has been identified as a prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the lipopolysaccharide (LPS)-induced sickness behavior in rats.MethodsAdult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally 1 h before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins.ResultsThe DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1β in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1.ConclusionsThese findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.
Highlights
Depression has been identified as a prevalent and severe mental disorder
The present study revealed that the sickness behaviors induced by LPS in rats are reversed by Dihydrolipoic acid (DHLA) treatment with the anti-depressant Flu and is associated with the upregulation of nuclear factor erythroid 2-like (Nrf2) and Heme oxygenase-1 (HO-1)
The inhibition of ERK abolished the preventive effect of DHLA, which was related to the low expression of Nrf2 and HO-1 and Statistical graphs of relative protein expression of Nrf2 (b), HO-1 (c), nod-like receptor pyrin-containing pyrin domain 3 (NLRP3) (d), caspase-1 (e), and IL-1β (f). g Reactive oxygen species (ROS) expression in the hippocampal
Summary
Depression has been identified as a prevalent and severe mental disorder. the mechanisms underlying the depression risk remain elusive. The limited therapies available for the treatment of this condition mainly target the monoamine levels. This approach is not efficient for many patients [1]. Despite that the specific regulatory mechanism of NLRP3 inflammasome activation is unclear, ROS has been frequently reported to be correlated with NLRP3 inflammasome activation [9, 10]. It regulates the expression and/ or activation of NLRP3 inflammasome in several diseases, including intestinal inflammation and cardiovascular disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
