[en] Both hypercortisolemia and hippocampal damage are features found in patients diagnosed of Alzheimer's disease (AD) and epidemiological evidence supports a role for stress as a risk factor for AD. It is known that immobilization stress is followed by accumulation of oxidative/nitrosative mediators in brain after the release of proinflammatory cytokines, nuclear factor kappa B activation, nitric oxide synthase-2 and cyclooxygenase-2 expression. Long-term exposure to elevated corticosteroid levels is known to affect the hippocampus which plays a central role in the regulation of the hypothalamic-pituitary-adrenal axis. We therefore studied the effect of chronic immobilization stress on amyloid precursor protein/PS1 mice. Stress exposure increased AD-induced neuroinflammation characterized by astrogliosis, increased inflammatory gene transcription and lipid peroxidation. Importantly, immobilization stress did not increase the soluble or insoluble amyloid β levels suggesting that increased cortisol levels lower the threshold for a neuroinflammatory response, independently from amyloid β. Since inflammation may act as a factor that contributes disease progression, the stress-inflammation relation described here may be relevant to understand the initial mechanisms in underlying the risk enhancing action of stress on AD.
Disciplines :
Neurology
Author, co-author :
Perez Nievas, Beatriz G; Department of Neurology, Clinical Neuroscience Unit, University of Bonn Medical Center, Bonn, Germany
Hammerschmidt, Thea; Department of Neurology, Clinical Neuroscience Unit, University of Bonn Medical Center, Bonn, Germany
Kummer, Markus P; Department of Neurology, Clinical Neuroscience Unit, University of Bonn Medical Center, Bonn, Germany
Terwel, Dick; Department of Neurology, Clinical Neuroscience Unit, University of Bonn Medical Center, Bonn, Germany
Leza, Juan C; Department of Pharmacology, Faculty of Medicine, Universidad Complutense, Madrid, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
HENEKA, Michael ; Department of Neurology, Clinical Neuroscience Unit, University of Bonn Medical Center, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Restraint stress increases neuroinflammation independently of amyloid β levels in amyloid precursor protein/PS1 transgenic mice.
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