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Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer's Disease Mouse Model.
J Alzheimers Dis. 2016; 49(2):301-16.JA

Abstract

It is unclear whether pre-symptomatic Alzheimer's disease (AD) causes circadian disruption or whether circadian disruption accelerates AD pathogenesis. In order to examine the sensitivity of learning and memory to circadian disruption, we altered normal lighting phases by an 8 h shortening of the dark period every 3 days (jet lag) in the APPSwDI NOS2-/- model of AD (AD-Tg) at a young age (4-5 months), when memory is not yet affected compared to non-transgenic (non-Tg) mice. Analysis of activity in 12-12 h lighting or constant darkness showed only minor differences between AD-Tg and non-Tg mice. Jet lag greatly reduced activity in both genotypes during the normal dark time. Learning on the Morris water maze was significantly impaired only in the AD-Tg mice exposed to jet lag. However, memory 3 days after training was impaired in both genotypes. Jet lag caused a decrease of glutathione (GSH) levels that tended to be more pronounced in AD-Tg than in non-Tg brains and an associated increase in NADH levels in both genotypes. Lower brain GSH levels after jet lag correlated with poor performance on the maze. These data indicate that the combination of the environmental stress of circadian disruption together with latent stress of the mutant amyloid and NOS2 knockout contributes to cognitive deficits that correlate with lower GSH levels.

Authors+Show Affiliations

Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School Medicine, Springfield, Illinois, USA.Department of Pharmacology, Southern Illinois University School Medicine, Springfield, Illinois, USA.Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School Medicine, Springfield, Illinois, USA. Department of Neurology, Southern Illinois University School Medicine, Springfield, Illinois, USA. Institute for Memory Impairment and Neurological Disorders (MIND), Department of Biomedical Engineering, University of California Irvine, Irvine, California, USA (current).

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26484899

Citation

LeVault, Kelsey R., et al. "Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift With Learning and Impaired Memory in an Alzheimer's Disease Mouse Model." Journal of Alzheimer's Disease : JAD, vol. 49, no. 2, 2016, pp. 301-16.
LeVault KR, Tischkau SA, Brewer GJ. Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer's Disease Mouse Model. J Alzheimers Dis. 2016;49(2):301-16.
LeVault, K. R., Tischkau, S. A., & Brewer, G. J. (2016). Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer's Disease Mouse Model. Journal of Alzheimer's Disease : JAD, 49(2), 301-16. https://doi.org/10.3233/JAD-150026
LeVault KR, Tischkau SA, Brewer GJ. Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift With Learning and Impaired Memory in an Alzheimer's Disease Mouse Model. J Alzheimers Dis. 2016;49(2):301-16. PubMed PMID: 26484899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer's Disease Mouse Model. AU - LeVault,Kelsey R, AU - Tischkau,Shelley A, AU - Brewer,Gregory J, PY - 2015/10/21/entrez PY - 2015/10/21/pubmed PY - 2016/9/13/medline KW - APPSwDI NOS2–/– KW - Alzheimer’s disease KW - GSH KW - circadian disruption KW - glutathione KW - jet lag KW - learning KW - memory KW - redox KW - sleep SP - 301 EP - 16 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 49 IS - 2 N2 - It is unclear whether pre-symptomatic Alzheimer's disease (AD) causes circadian disruption or whether circadian disruption accelerates AD pathogenesis. In order to examine the sensitivity of learning and memory to circadian disruption, we altered normal lighting phases by an 8 h shortening of the dark period every 3 days (jet lag) in the APPSwDI NOS2-/- model of AD (AD-Tg) at a young age (4-5 months), when memory is not yet affected compared to non-transgenic (non-Tg) mice. Analysis of activity in 12-12 h lighting or constant darkness showed only minor differences between AD-Tg and non-Tg mice. Jet lag greatly reduced activity in both genotypes during the normal dark time. Learning on the Morris water maze was significantly impaired only in the AD-Tg mice exposed to jet lag. However, memory 3 days after training was impaired in both genotypes. Jet lag caused a decrease of glutathione (GSH) levels that tended to be more pronounced in AD-Tg than in non-Tg brains and an associated increase in NADH levels in both genotypes. Lower brain GSH levels after jet lag correlated with poor performance on the maze. These data indicate that the combination of the environmental stress of circadian disruption together with latent stress of the mutant amyloid and NOS2 knockout contributes to cognitive deficits that correlate with lower GSH levels. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26484899/Circadian_Disruption_Reveals_a_Correlation_of_an_Oxidative_GSH/GSSG_Redox_Shift_with_Learning_and_Impaired_Memory_in_an_Alzheimer's_Disease_Mouse_Model_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-150026 DB - PRIME DP - Unbound Medicine ER -