Keywords

Sleep, TNFα, siRNA, gluR; interleukin-6, EEG, cytokine

Abstract

Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNFα were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNFα siRNA treatment specifically reduced TNFα mRNA by 45% in vitro without affecting interleukin-6 or gluR1-4 mRNA levels. In vivo the TNFα siRNAα reduced TNFα mRNA, interleukin-6 mRNA and gluR1 mRNA levels compared to treatment with a scrambled control siRNA. After in vivo microinjection, the density of TNFα-immunoreactive cells in layer V of the SSctx was also reduced. Electroencephalogram (EEG) delta wave power was decreased on days 2 and 3 on the side of the brain that received the TNFα siRNA microinjection relative to the side receiving the control siRNA. These findings support the hypothesis that TNFα siRNA attenuates TNFα mRNA and TNFα protein in the rat cortex and that those reductions reduce cortical EEG delta power. Results also are consistent with the notion that TNFα is involved in CNS physiology including sleep regulation.

Original Publication Citation

Taishi P, Churchill L, Wang M, Kay D, Davis CJ, Guan X, De A, Yasuda T, Liao F, Krueger JM. TNFalpha siRNA reduces brain TNF and EEG delta wave activity in rats. Brain Res. 2007;1156:125-132. PMCID: PMC2041959.

Document Type

Peer-Reviewed Article

Publication Date

2008-07-02

Publisher

Brain Res.

Language

English

College

Family, Home, and Social Sciences

Department

Psychology

University Standing at Time of Publication

Associate Professor

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Psychology Commons

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