Decrease of DISC1 gene expression is associated with increase of GSK3Beta expression and memory loss of mice upon aging [Farelerde DISC1 gen azlığı ile GSK3Beta fazlalığı yaşlılıktaki bellek yitiminde birliktedir]

Background: age-related memory loss is quite common in the elderly. with the increase of aged population,this problem is becoming more and more severe. the effective treatment is currently unavailable because of the lack of understanding of the underlying molecular mechanisms. the present study aimed to explore the mechanism underlying memory impairment in aged mice. methods: y-maze spontaneous alternation paradigm and olfactory memory test were employed to examine the memory in aged mice. rt-pcr and western blot were used to detect the expression of disc1 and gsk3β expression in the hippocampus and cultured hippocampal neurons,in which disc1 was overexpressed and knocked down using viral transfection and sirna techniques,respectively. results: the memory was greatly impaired in aged mice. disc1 expression was greatly decreased,whereas the expression of gsk3β was dramatically increased in the hippocampus of old mice as compared to young mice. the memory impairment in old mice is highly correlated with decreased expression of disc1 and increased expression of gsk3β. furthermore,over expression of disc1 in cultured hippocampal neurons resulted in decreased gsk3β expression,whereas knockdown of disc1 increased gsk3β expression in neuronal and glial cell lines. conclusion: taken together,these results suggest that decrease of disc1 expression and the subsequent increase of gsk3β expression may contribute to the memory loss upon aging. © 2015,ege university press. all rights reserved.