Transforming growth factor-beta inhibits the expression of clock genes

被引：22

作者：

Gast, Heidemarie ^{[3
]}

Gordic, Sonja ^{[1
]}

Petrzilka, Saskia ^{[1
]}

Lopez, Martin ^{[1
]}

Mueller, Andreas ^{[1
]}

Gietl, Anton ^{[2
]}

Hock, Christoph ^{[2
]}

Birchler, Thomas ^{[1
]}

Fontana, Adriano ^{[1
]}

机构：

[1] Univ Zurich, Inst Expt Immunol, CH-8057 Zurich, Switzerland

[2] Univ Zurich, Div Psychiat Res, CH-8057 Zurich, Switzerland

[3] Univ Bern, Inselspital, Dept Neurol, Univ Hosp Bern, CH-3010 Bern, Switzerland

来源：

NEUROIMMUNOMODULATION IN HEALTH AND DISEASE I | 2012年 / 1261卷

基金：

瑞士国家科学基金会;

关键词：

sleep genes; memory; sleep deprivation; E-box; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; TGF-BETA; TRANSCRIPTIONAL REPRESSOR; MEMORY CONSOLIDATION; RETROGRADE-AMNESIA; TGF-BETA-1; DEC1; TIME;

D O I：

10.1111/j.1749-6632.2012.06640.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Disturbances of sleep-wake rhythms are an important problem in Alzheimer's disease (AD). Circadian rhythms are regulated by clock genes. Transforming growth factor-beta (TGF-beta) is overexpressed in neurons in AD and is the only cytokine that is increased in cerebrospinal fluid (CSF). Our data show that TGF-beta 2 inhibits the expression of the clock genes Period (Per) 1, Per2, and Rev-erb alpha, and of the clock-controlled genes D-site albumin promoter binding protein (Dbp) and thyrotroph embryonic factor (Tef). However, our results showed that TGF-beta 2 did not alter the expression of brain and muscle Arnt-like protein-1 (Bmal1). The concentrations of TGF-beta 2 in the CSF of 2 of 16 AD patients and of 1 of 7 patients with mild cognitive impairment were in the dose range required to suppress the expression of clock genes. TGF-beta 2-induced dysregulation of clock genes may alter neuronal pathways, which may be causally related to abnormal sleep-wake rhythms in AD patients.

引用

页码：79 / 87

页数：9

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