The Role Of Insulin/IGF-1 Signaling Pathway In The Pathogenesis Of Cognitive Dysfunction

PurposeBy observing the learning and memory function of C57 mice at different ages and the changes of serum IGF-1,the relationship between age and cognitive impairment was further discussed,and the effect of insulin/IGF-1 level on cognitive function was studied,so as to prevent and delay the cognitive impairment in the population with high-risk cognitive impairment.MethodsC57 mice were divided into 2 months,6 months,9 months,12 months,18 months and 24 months of age,respectively.A series of learning and memory performance tests were conducted,including Morris water maze,Y maze,Elevated plus maze,Forced swim test,and Locomotor Activity.The changes of C57 mice of different ages(2,6,9,12,18,24 months)in spatial learning and memory,emotional learning and memory,as well as recognition memory and working memory were compared.Serum IGF-1 levels in mice of different ages were detected by enzyme-linked immunoassay(ELISA).Result1.With the increase of age,the serum IGF-1 level of mice first increased and then decreased,the expression level of 2-month old mice(childhood)was low,the expression level of 6-month old mice(youth)reached a peak,and maintained to 9 months old,then gradually decreased,and decreased significantly to 24 months old(old age).Slight statistical difference(P=0.0457).2.In the Morris water maze experiment,with the extension of the training time,the incubation period of the mice at all ages,that is,the time to find the platform,was gradually shortened,and the time,distance and the number of times the mice explored in the third quadrant and crossed the platform were gradually reduced,in which the time and distance were statistically different(P<0.01).In the Y maze experiment,the accuracy of 5min and 8min was gradually reduced,and there was a statistical difference(P<0.0001),indicating that the recognition and memory ability of the mice was gradually decreased with age.In the viaduct maze experiment,the mice showed obvious anxiety from infancy to youth,and gradually reduced in old age,with statistical difference(P<0.001).In the forced swimming experiment,there was no statistical difference in depression-like behavior with the aging of mice(P>0.05).In the spontaneous activity experiment,with the increase of age,the activity of mice presented a gradually declining trend,and there was a statistical difference(P=0.0239).Conclusions(1)With the increase of age,the learning and memory ability of mice decreased.(2)Serum IGF-1 level in mice gradually increased and reached a peak from infancy to youth,then gradually decreased after youth and significantly decreased in old age,which may be related to age-related cognitive function.