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Restraint stress increases neuroinflammation independently of amyloid β levels in amyloid precursor protein/PS1 transgenic mice
Author(s) -
Perez Nievas Beatriz G.,
Hammerschmidt Thea,
Kummer Markus P.,
Terwel Dick,
Leza Juan C.,
Heneka Michael T.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07083.x
Subject(s) - neuroinflammation , endocrinology , amyloid precursor protein , proinflammatory cytokine , oxidative stress , astrogliosis , medicine , neurodegeneration , inflammation , hippocampus , alzheimer's disease , central nervous system , disease
J. Neurochem. (2011) 116, 43–52. Abstract 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.