کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6808745 | 1433593 | 2012 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Combination therapy prevents amyloid-dependent and -independent structural changes
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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
Neuropathological features of Alzheimer's disease (AD) are recapitulated in transgenic mice expressing familial AD-causing mutations, but ectopic transgene overexpression makes it difficult to relate these abnormalities to disease pathogenesis. Alternatively, the APP/PS-1 double knock-in (DKI) mouse produces mutant amyloid precursor protein (APP) and presenilin-1 (PS-1) with normal levels and regulatory controls. Here, we investigated effects of amyloid on brain structure and neuroplasticity by vaccinating DKI mice with amyloid-β starting at 8 months of age. At 14 months, vaccination blocked cerebral amyloid deposition and its attendant microglial activation. Neuropil abnormalities were pronounced only within plaques, and included circumscribed loss and dysmorphology of axons, dendrites, terminals and spines. Blockade of amyloid deposition restored neuropil integrity. Amyloid removal did not rescue reductions in the hippocampal neural progenitor and neuroblast populations, but adding 1 month of voluntary exercise to amyloid-β vaccination markedly stimulated hippocampal neurogenesis. These results identify amyloid-dependent and -independent structural changes in the DKI mouse model of AD. Combining exercise with amyloid-directed immunotherapy produces greater restoration of brain structure and neuroplasticity than is achieved with either maneuver alone.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 33, Issue 7, July 2012, Pages 1273-1283
Journal: Neurobiology of Aging - Volume 33, Issue 7, July 2012, Pages 1273-1283
نویسندگان
Gauri Malthankar-Phatak, Shane Poplawski, Nikhil Toraskar, Robert Siman,