Overexpression Of ApoE4(1-272) Can Induce The Spatial Memory Impairment Of Rats By Triggering The ER Stress.

Aim Human apolipoprotein (apo) E4 is one of proverbial major risk factors for Alzheimer's disease (AD). Studies suggested that truncated-apoE4 fragments apoE4(1-272) take part in the pathology process of AD. However, the mechanism of increasing the risk of AD and its role in the pathogenesis of AD are not fully understood. We investigate whether apoE4(1-272) induces the spatial memory impairment of rats by triggering the endoplasmic reticulum stress (ERS) in rat hippocampus.Methods SD rats were divided into two groups, sham group, apoE4(1-272) transfection group . At 48 hours after transfection, fluorescence microscope detected the florescence. 24 male SD rats were randomly divided into four groups, control group, pEGFP transfection group, apoE4(1-272) transfection group and 4-PBA treatment group.The rats of 4-PBA group have been injected 4-PBA (1g/kg/day) by using the stomach tube for 12 weeks before apoE4(1-272) transfection to the hippocampus by stereotaxis instrument, then continue to be lavaged. At 48-72 hours after transfection, the rat's hippocampus were harvested for analyses of the expression of ApoE4(1-272) and ERS marker GRP78 by fluorescence microscopy and Western blot. At one week after transfection, Morris water maze was used to test the spatial reference memory of these rats. Results The results of fluorescence microscopy and Western blot indicated that the ApoE4(1-272) could be located and expressed in the rats hippocampus through stereotaxis instrument. The results of Western blot showed that the overexpression of ApoE4(1-272) induced the increase of GRP78 expression in the hippocampus. This effect was inhibited by the pretreatment of 4-PBA significantly(P<0.01). The data of Morris water maze exhibited that the overexpression of ApoE4(1-272) in the hippocampus impaired the ability of rat's spatial reference memory significantly(P<0.01). 4-PBA could reduce the impairment of the spatial reference memory induced by ApoE4(1-272) overexpression in the hippocampus significantly(P<0.01).Conclusions Overexpression of ApoE4(1-272) in rat hippocampus can induce the spatial memory impairment of rats by triggering the ER stress.