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Transforming growth factor‐beta inhibits the expression of clock genes
Author(s) -
Gast Heidemarie,
Gordic Sonja,
Petrzilka Saskia,
Lopez Martin,
Müller Andreas,
Gietl Anton,
Hock Christoph,
Birchler Thomas,
Fontana Adriano
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06640.x
Subject(s) - per2 , clock , medicine , endocrinology , circadian rhythm , biology , transforming growth factor , circadian clock , transforming growth factor beta
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‐β) is overexpressed in neurons in AD and is the only cytokine that is increased in cerebrospinal fluid (CSF). Our data show that TGF‐β2 inhibits the expression of the clock genes Period ( Per ) 1 , Per2, and Rev‐erbα , and of the clock‐controlled genes D‐site albumin promoter binding protein ( Dbp) and thyrotroph embryonic factor ( Tef ). However, our results showed that TGF‐β2 did not alter the expression of brain and muscle Arnt‐like protein‐1 ( Bmal1 ). The concentrations of TGF‐β2 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‐β2–induced dysregulation of clock genes may alter neuronal pathways, which may be causally related to abnormal sleep–wake rhythms in AD patients.