Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle

被引：1107

作者：

Kang, Jae-Eun ^{[1
]}

Lim, Miranda M. ^{[1
]}

Bateman, Randall J. ^{[1
,2
,3
]}

Lee, James J. ^{[1
]}

Smyth, Liam P. ^{[1
]}

Cirrito, John R. ^{[1
,2
]}

Fujiki, Nobuhiro ^{[4
]}

Nishino, Seiji ^{[4
]}

Holtzman, David M. ^{[1
,2
,3
,5
]}

机构：

[1] Washington Univ, Dept Neurol, St Louis, MO 63110 USA

[2] Washington Univ, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[3] Washington Univ, Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

[4] Stanford Univ, Sleep & Circadian Neurobiol Lab, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA

[5] Washington Univ, Dept Dev Biol, St Louis, MO 63110 USA

来源：

SCIENCE | 2009年 / 326卷 / 5955期

关键词：

NEUROBIOLOGY; DROSOPHILA; PLAQUES; SYSTEMS; NEURONS; MICE;

D O I：

10.1126/science.1180962

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid-beta (A beta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. A beta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of A beta. Using in vivo microdialysis in mice, we found that the amount of ISF A beta correlated with wakefulness. The amount of ISF A beta also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, A beta plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease.

引用

页码：1005 / 1007

页数：3

共 14 条

[1] Synaptic activity regulates interstitial fluid amyloid-β levels in vivo [J].

Cirrito, JR ;

Yamada, KA ;

Finn, MB ;

Sloviter, RS ;

Bales, KR ;

May, PC ;

Schoepp, DD ;

Paul, SM ;

Mennerick, S ;

Holtzman, DM .

NEURON, 2005, 48 (06) :913-922

[2] Use-Dependent Plasticity in Clock Neurons Regulates Sleep Need in Drosophila [J].

Donlea, Jeffrey M. ;

Ramanan, Narendrakumar ;

Shaw, Paul J. .

SCIENCE, 2009, 324 (5923) :105-108

[3] Neurobiology of Sleep Disturbances in Neurodegenerative Disorders [J].

Gagnon, J. -F. ;

Petit, D. ;

Latreille, V. ;

Montplaisir, J. .

CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (32) :3430-3445

[4] Widespread Changes in Synaptic Markers as a Function of Sleep and Wakefulness in Drosophila [J].

Gilestro, Giorgio F. ;

Tononi, Giulio ;

Cirelli, Chiara .

SCIENCE, 2009, 324 (5923) :109-112

[5] Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice [J].

Hsiao, K ;

Chapman, P ;

Nilsen, S ;

Eckman, C ;

Harigaya, Y ;

Younkin, S ;

Yang, FS ;

Cole, G .

SCIENCE, 1996, 274 (5284) :99-102

[6] Arousal effect of orexin A depends on activation of hte histmic system [J].

Huang, ZL ;

Qu, WM ;

Li, WD ;

Mochizuki, T ;

Eguchi, N ;

Watanabe, T ;

Urade, Y ;

Hayaishi, O .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9965-9970

[7] APP processing and synaptic function [J].

Kamenetz, F ;

Tomita, T ;

Hsieh, H ;

Seabrook, G ;

Borchelt, D ;

Iwatsubo, T ;

Sisodia, S ;

Malinow, R .

NEURON, 2003, 37 (06) :925-937

[8] Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity [J].

Kang, Jae-Eun ;

Cirrito, John R. ;

Dong, Hongxin ;

Csernansky, John G. ;

Holtzman, David M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (25) :10673-10678

[9] New Developments in Sleep Research: Molecular Genetics, Gene Expression, and Systems Neurobiology [J].

Kilduff, Thomas S. ;

Lein, Ed S. ;

de la Iglesia, Horacio ;

Sakurai, Takeshi ;

Fu, Ying-Hui ;

Shaw, Paul .

JOURNAL OF NEUROSCIENCE, 2008, 28 (46) :11814-11818

[10]

Peyron C, 1998, J NEUROSCI, V18, P9996

← 1 2 →