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Augmentation by Hypercholesterolemia of Amyloid β Peptide-Induced Learning and Memory Deficit
Yun-Bae Kim,Dongsun Park,Jiyoung Oh,Tae Kyun Kim,Young Jin Cho,Sun Hee Lee,Dae-Kwon Bae,Yun-Hui Yang,Goeun Yang,Seock-Yeon Hwang 충북대학교 동물의학연구소 2009 Journal of Biomedical and Translational Research Vol.10 No.2
The present study was carried out to establish an animal model, displaying long-term learning and memory dysfunction, since single intracerebroventricular (icv) injection of amyloid β peptide (Aβ) causes a short-term memory impairment. Male ICR mice were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 1% corn oil and 0.5% cholic acid, and 1 week later, icv injected with Aβ<sub>1-42</sub> (5 μg/head). Learning/ memory function was assessed via passive avoidance performances 1 day and 2, 4, and 6 weeks after Aβ<sub>1-42</sub> injection, in addition to blood biochemical analyses for lipid profiles and hepatic function. Total cholesterol, lowdensity lipoproteins and hepatic dysfunction parameters markedly increased, while high-density lipoproteins were reduced following HCD feeding. Whereas single injection of Aβ induced temporary memory loss 1 day after administration, exhibiting full recovery after 2 weeks, Aβ treatment in combination with HCD feeding lasted the learning/memory impairment up to 6 weeks. Therefore, it is suggested that hypercholesterolemia augments Aβ-induced memory loss, and that Aβ injection plus HCD feeding could be a long-term memorydeficit model suitable for long-term treatment with drugs or stem cells.