Small dose of L-dopa/Benserazide hydrochloride improved sepsis-induced neuroinflammation and long-term cognitive dysfunction in sepsis mice

Abstract

The prevention and treatment of sepsis associated encephalopathy (SAE) remains challenging in clinic. Besides the anti-infection treatments and goal-directed supportive treatments, no specific method is reported for the prevention and treatment of SAE. This study tried to investigate the effects and underlying mechanisms of small dose of L-dopa/Benserazide hydrochloride (L-DA) on SAE. We found that L-DA administration (i.p.) at early stage of sepsis, but not at late stage, improved learning and memory of sepsis surviving mice in Cecal ligation and perforation (CLP) model. Corresponding to the improvement of learning and memory in CLP model, L-DA administration limited neuroinflammation, improved neuroplasticity, reversed sepsis-induced decrease of hippocampal dopamine level, but had no obvious effects on the survival and body weight recovery. Further studies showed that specific inhibitors of dopamine D1 or D2 receptors both partly reduced the protective effect of L-DA on the learning and memory of lipopolysaccharides (LPS) treated mice. D1 receptor specific inhibitor significantly blocked the anti-neuroinflammation effects of L-DA in LPS treated mice, but D2 receptor inhibitor did not. All these suggest that L-DA administration could prevent and treat SAE via dopamine D1 and D2 receptors. Dopamine D1 receptor is a potential target of anti-neuroinflammation.

Keywords: Cognitive function; D1 receptor; L-dopa; Neuroinflammation; Sepsis-associated encephalopathy.