Chronic N-acetylcysteine Exposure Improves The Working Memory Impairment Induced By Acute Lipopolysaccharide Through Up Regulation Of Caveolin-1 And Synaptophysin

Working memory is a dynamic coding information and in a short time active reproduction process.The prefrontal cortex region dominates the cognitive function of the key role is working memory.A large number of studies have shown that both the human and animal’s prefrontal cortex lesions are affected by varying degrees of behavioral changes,mainly including working memory,attention and behavioral inhibition and other functional damage.When the working memory is affected by various factors,for example,inflammation,oxidative free radicals and other stimulis,by the working memory of the upcoming performance capacity is destroyed.Lipopolysaccharide(LPS)is the main component of the cell wall of Gram-negative bacteria,and has the proinflammatory effect after infection.N-acetylcysteine(NAC)is a precursor of glutathione as a small molecule that is free to enter the cytoplasm through the cell membrane.In patients with neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,schizophrenia and so on.NAC has an ideal anti-inflammatory and anti-oxidative effects.Under glucose and hypoxia,NAC can reduce oxidative stress and prevent damage to the working memory of space,thereby improving learning and memory.At the same time,NAC can protect neuronal synaptic activity,with neuroprotective effect.In this study,NAC pretreatment was used to explore the mechanism of endotoxin-induced neuronal inflammation leading to working memory impairment and its potential molecular mechanism.Objective:To study the effect of NAC pretreatment on working memory and the specific molecular mechanism under the condition of acute LPS-induced working memory injury.Methods:(1)The animals were randomly divided into three groups:vehicle + LPS group,(3)NAC + LPS group,(4)NAC group.Delayed T maze training,the mice first control the diet(2.5g each day)a week,so that the body weight to about 85%of the original weight,at the same time using intraperitoneal injection of NAC(100mg/kg).A week later began to delay the T maze alternate task training until the correct rate of choice in the T maze alternately began to detect 80%for 3 days,this process continued to control the diet and intraperitoneal injection of NAC(100mg/kg)one week.Delayed T maze alternation was performed 4 hours prior to intraperitoneal injection of LPS(0.5mg/kg).Results:(1)Acute LPS treatment,causing working memory impairment in the delayed T maze task,NAC treatment can prevent LPS caused by working memory damage in mice.(2)LPS could down-regulate the expression of Cav-1 and SYP in the prefrontal cortex of mice,while NAC could reverse the decrease of Cav-1 and SYP,and prevent working memory damage in delay T maze alternating task.Conclusion:Acute injection of LPS induced memory impairment in mice and associated with down-regulation of Cav-1 and SYP expression,and NAC pretreatment significantly inhibited LPS induced decrease in Cav-1 and SYP,and improved working memory impairment.