Transforming growth factor-beta inhibits the expression of clock genes

Gast, Heidemarie; Gordic, Sonja; Petrzilka, Saskia; Lopez, Martin; Müller, Andreas; Gietl, Anton; Hock, Christoph; Birchler, Thomas; Fontana, Adriano (2012). Transforming growth factor-beta inhibits the expression of clock genes. Annals of the New York Academy of Sciences, 1261(1), pp. 79-87. Boston, Mass.: Blackwell 10.1111/j.1749-6632.1990.tb16121.x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Gast, Heidemarie

ISSN:

0077-8923

Publisher:

Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:26

Last Modified:

05 Dec 2022 14:08

Publisher DOI:

10.1111/j.1749-6632.1990.tb16121.x

PubMed ID:

22823397

Web of Science ID:

000312537900012

URI:

https://boris.unibe.ch/id/eprint/9461 (FactScience: 215198)

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