Effect of ASX on chronic alcoholism induced memory impairment and expressions of NF-κB p65,iNOS,TNF-αin mice / 中国药理学通报

ABSTRACT

Aim To investigate the effect of ASX (trans-astaxanthin)on the expressions of NF-κB p65 , iNOS and TNF-αin the hippocampus and the prefron-tal cortex of chronic alcohol mice.Methods 40 mice were randomly divided into control group,7 d,14 d, 21 d,28 d alcohol-treated group,the mice were given alcohol preference testing on day of 6,13,20,27. Mice were subjected to alcohol withdrawal for one day after testing.In order to determine the exact time point of cognitive memory impairment in mice after alcohol consumption,they were given morris water maze test after alcohol preference testing. The other 40 mice were randomly divided into control group, alcohol group and ASX group (20,40,80 mg·kg-1 ).After chronic ASX administration, mice were given one probe trial of 60 s in which the platform was removed from the pool to evaluate escape latency,the number of times the animal crossed the previous location of the platform,time spent in the target quadrant,and swim-ming speed.The expressions of NF-κB p65 ,iNOS and TNF-αwere detected by western blotting after behav-ioral testing.Results The mice showed an obvious al-cohol-related phenomenon on 2 1 and 28 days after al-cohol treatment,and escape latency significantly in-creased,entries in target quadrant and duration in tar-get quadrant significantly decreased with increasing drinking days and withdrawal times.The results also suggested that 2 1 days chronic ASX treatment reversed this learning deficit.Moreover,the expression of NF-κB p65 ,iNOS and TNF-αin the hippocampus were significantly increased after 2 1 d alcohol treatment (P<0.001),and pretreatment with ASX (40,80 mg· kg-1 ) could obviously inhibit these changes (P <0.001);Parallel to these changes in the hippocam-pus,the level of NF-κB p65 ,iNOS and TNF-αwere also increased in the prefrontal cortex (P<0.001 ), however,only ASX (80 mg · kg-1 ) administration could inhibit the increase (P<0.05 ).Conclusion These results indicate that ASX pretreatment can pro-tect against alcohol-induced memory impairment via the inhibition of NF- κB p65 ,iNOS and TNF-αexpres-sions in hippocampus and prefrontal cortex.