دورية أكاديمية
The amyloidogenic potential and behavioral correlates of stress
| العنوان: | The amyloidogenic potential and behavioral correlates of stress |
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| المؤلفون: | Catania, C., Sotiropoulos, I., Silva, R., Onofri, C., Breen, K. C., Sousa, Nuno, Almeida, O. F. X. |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2009 |
| المجموعة: | Universidade of Minho: RepositóriUM |
| مصطلحات موضوعية: | Amyloid beta-Protein Precursor, Analysis of Variance, Animals, Behavior, Animal, Disease Models, Emotions, Glucocorticoids, Hippocampus, Male, Memory, Prefrontal Cortex, Rats, Wistar, Space Perception, Stress, Psychological, Alzheimer’s disease, Amyloid precursor protein, Amyloid-b, Anxiety, Amyloid-β, Science & Technology |
| الوصف: | Observations of elevated basal cortisol levels in Alzheimer's disease (AD) patients prompted the hypothesis that stress and glucocorticoids (GC) may contribute to the development and/or maintenance of AD. Consistent with that hypothesis, we show that stress and GC provoke misprocessing of amyloid precursor peptide in the rat hippocampus and prefrontal cortex, resulting in increased levels of the peptide C-terminal fragment 99 (C99), whose further proteolytic cleavage results in the generation of amyloid-beta (Abeta). We also show that exogenous Abeta can reproduce the effects of stress and GC on C99 production and that a history of stress strikingly potentiates the C99-inducing effects of Abeta and GC. Previous work has indicated a role for Abeta in disruption of synaptic function and cognitive behaviors, and AD patients reportedly show signs of heightened anxiety. Here, behavioral analysis revealed that like stress and GC, Abeta administration causes spatial memory deficits that are exacerbated by stress and GC; additionally, Abeta, stress and GC induced a state of hyperanxiety. Given that the intrinsic properties of C99 and Abeta include neuroendangerment and behavioral impairment, our findings suggest a causal role for stress and GC in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy can have a cumulative impact on the course of AD development and progression. ; CC and IS were supported by stipends from the Max Planck Society and EU Marie Curie Training Fellowships (at University College London, UK). The collaboration between the German and Portuguese laboratories was supported through the German–Portuguese Luso-Alemas Program (DAAD/GRICES). This study was conducted within the framework of the EU-supported integrated project ‘CRESCENDO’ (Contract FP6-018652). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1359-4184 1476-5578 |
| العلاقة: | DAAD/GRICES; FP6-018652; https://www.nature.com/articles/4002101Test; http://hdl.handle.net/1822/64301Test |
| DOI: | 10.1038/sj.mp.4002101 |
| الإتاحة: | https://doi.org/10.1038/sj.mp.4002101Test http://hdl.handle.net/1822/64301Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.60FDEBB5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13594184 14765578 |
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| DOI: | 10.1038/sj.mp.4002101 |