کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6806984 | 1433577 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reduced plasticity and mild cognitive impairment-like deficits after entorhinal lesions in hAPP/APOE4 mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Mild cognitive impairment (MCI) is a clinical condition that often precedes Alzheimer disease (AD). Compared with apolipoprotein E-ε3 (APOE3), the apolipoprotein E-ε4 (APOE4) allele is associated with an increased risk of developing MCI and spatial navigation impairments. In MCI, the entorhinal cortex (EC), which is the main innervation source of the dentate gyrus, displays partial neuronal loss. We show that bilateral partial EC lesions lead to marked spatial memory deficits and reduced synaptic density in the dentate gyrus of APOE4 mice compared with APOE3 mice. Genotype and lesion status did not affect the performance in non-navigational tasks. Thus, partial EC lesions in APOE4 mice were sufficient to induce severe spatial memory impairments and synaptic loss in the dentate gyrus. In addition, lesioned APOE4 mice showed no evidence of reactional increase in cholinergic terminals density as opposed to APOE3 mice, suggesting that APOE4 interferes with the ability of the cholinergic system to respond to EC input loss. These findings provide a possible mechanism underlying the aggravating effect of APOE4 on the cognitive outcome of MCI patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 34, Issue 11, November 2013, Pages 2683-2693
Journal: Neurobiology of Aging - Volume 34, Issue 11, November 2013, Pages 2683-2693
نویسندگان
Jean-Bastien Bott, Brigitte Cosquer, Céline Héraud, Celina Zerbinatti, Christian Kelche, Jean-Christophe Cassel, Chantal Mathis,