Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.
Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.
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DOI：
10.1016/j.bbi.2014.09.005
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发表时间：
2015-07
影响因子：
15.1
通讯作者：
Holtzman, David M.
中科院分区：
文献类型：
--
作者：
Liao, Fan;Zhang, Tony J.;Mahan, Thomas E.;Jiang, Hong;Holtzman, David M.
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHRlit/lit mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHRlit/lit mice was significantly smaller than that in PS1APP/GHRHRlit/+ mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition.
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影响因子：
5.6
作者：
Naylor, Erik;Aillon, Daniel V.;Petillo, Peter A.
通讯作者：
Petillo, Peter A.
DOI：
10.18632/aging.100504
发表时间：
2012-11
期刊：
Aging
影响因子：
--
作者：
Jaszberenyi M;Rick FG;Szalontay L;Block NL;Zarandi M;Cai RZ;Schally AV
通讯作者：
Schally AV
DOI：
10.1126/science.1180962
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kang JE;Lim MM;Bateman RJ;Lee JJ;Smyth LP;Cirrito JR;Fujiki N;Nishino S;Holtzman DM
通讯作者：
Holtzman DM
影响因子：
4.7
作者：
Dash, Michael B.;Bellesi, Michele;Cirelli, Chiara
通讯作者：
Cirelli, Chiara
影响因子：
5.3
作者：
Liao, Fan;Ping Taishi;Krueger, James M.
通讯作者：
Krueger, James M.