Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease

Ardiles á.O.; Tapia-Rojas C.C.; Mandal M.Alexandre F.Kirkwood A.Inestrosa N.C.Palacios A.G.

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Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease

机译：Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease

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Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-a (Aa) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aa oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aa oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aa oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第34期|13835-13840|共6页
作者
Ardiles á.O.; Tapia-Rojas C.C.; Mandal M.Alexandre F.Kirkwood A.Inestrosa N.C.Palacios A.G.;
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作者单位

Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile;

Centro de Envejecimiento Y Regeneración, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331010 Santiago, Chile;

Mind/Brain Institute, Department of Neurosciences, Johns Hopkins University, Baltimore, MD 21218, United StatesInstitut des Maladies Neurodégénératives, Department Mnemosyne, Centre de Recherche Inria Bordeaux, F-33076 Bordeaux, France;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Aging; Hippocampus; Memory dysfunction; Neural plasticity; T-maze;

Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease

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