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Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress.
J Neurochem 2009; 108(1):165-75JN

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by genetic and non-genetic factors. Most AD cases may be triggered and promoted by non-genetic environmental factors. Clinical studies have reported that patients with AD show enhanced baseline levels of stress hormones in the blood, but their physiological significance with respect to the pathophysiology of AD is not clearly understood. Here we report that AD mouse models exposed to restraints for 2 h daily on 16 consecutive days show increased levels of beta-amyloid (Abeta) plaque deposition and commensurable enhancements in Abeta(1-42), tau hyperphosphorylation, and neuritic atrophy of cortical neurons. Repeated restraints in Tg2576 mice markedly increased metabolic oxidative stress and down-regulated the expression of MMP-2, a potent Abeta-degrading enzyme, in the brain. These stress effects were reversed by blocking the activation of the hypothalamus-pituitary-adrenal gland axis with the corticotropin-releasing factor receptor antagonist NBI 27914, further suggesting that over-activation of the hypothalamic-pituitary-adrenal axis is required for stress-enhanced AD-like pathogenesis. Consistent with these findings, corticosteroid treatments to cultured primary cortical neurons increased metabolic oxidative stress and down-regulated MMP-2 expression, and MMP-2 down-regulation was reversed by inhibition of oxidative stress. These results suggest that behavioral stress aggravates AD pathology via generation of metabolic oxidative stress and MMP-2 down-regulation.

Authors+Show Affiliations

Division of Nano Sciences and Brain Disease Research Institute, Ewha Womans University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19012747

Citation

Lee, Kang-Woo, et al. "Behavioral Stress Accelerates Plaque Pathogenesis in the Brain of Tg2576 Mice Via Generation of Metabolic Oxidative Stress." Journal of Neurochemistry, vol. 108, no. 1, 2009, pp. 165-75.
Lee KW, Kim JB, Seo JS, et al. Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. J Neurochem. 2009;108(1):165-75.
Lee, K. W., Kim, J. B., Seo, J. S., Kim, T. K., Im, J. Y., Baek, I. S., ... Han, P. L. (2009). Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. Journal of Neurochemistry, 108(1), pp. 165-75. doi:10.1111/j.1471-4159.2008.05769.x.
Lee KW, et al. Behavioral Stress Accelerates Plaque Pathogenesis in the Brain of Tg2576 Mice Via Generation of Metabolic Oxidative Stress. J Neurochem. 2009;108(1):165-75. PubMed PMID: 19012747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. AU - Lee,Kang-Woo, AU - Kim,Jung-Bin, AU - Seo,Ji-Seon, AU - Kim,Tae-Kyung, AU - Im,Joo-Young, AU - Baek,In-Sun, AU - Kim,Kyoung-Shim, AU - Lee,Ja-Kyeong, AU - Han,Pyung-Lim, Y1 - 2008/11/21/ PY - 2008/11/18/pubmed PY - 2009/4/9/medline PY - 2008/11/18/entrez SP - 165 EP - 75 JF - Journal of neurochemistry JO - J. Neurochem. VL - 108 IS - 1 N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by genetic and non-genetic factors. Most AD cases may be triggered and promoted by non-genetic environmental factors. Clinical studies have reported that patients with AD show enhanced baseline levels of stress hormones in the blood, but their physiological significance with respect to the pathophysiology of AD is not clearly understood. Here we report that AD mouse models exposed to restraints for 2 h daily on 16 consecutive days show increased levels of beta-amyloid (Abeta) plaque deposition and commensurable enhancements in Abeta(1-42), tau hyperphosphorylation, and neuritic atrophy of cortical neurons. Repeated restraints in Tg2576 mice markedly increased metabolic oxidative stress and down-regulated the expression of MMP-2, a potent Abeta-degrading enzyme, in the brain. These stress effects were reversed by blocking the activation of the hypothalamus-pituitary-adrenal gland axis with the corticotropin-releasing factor receptor antagonist NBI 27914, further suggesting that over-activation of the hypothalamic-pituitary-adrenal axis is required for stress-enhanced AD-like pathogenesis. Consistent with these findings, corticosteroid treatments to cultured primary cortical neurons increased metabolic oxidative stress and down-regulated MMP-2 expression, and MMP-2 down-regulation was reversed by inhibition of oxidative stress. These results suggest that behavioral stress aggravates AD pathology via generation of metabolic oxidative stress and MMP-2 down-regulation. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/19012747/Behavioral_stress_accelerates_plaque_pathogenesis_in_the_brain_of_Tg2576_mice_via_generation_of_metabolic_oxidative_stress_ L2 - https://doi.org/10.1111/j.1471-4159.2008.05769.x DB - PRIME DP - Unbound Medicine ER -