title: Cytokine-induced sleep: Neurons respond to TNF with production of chemokines and increased expression of Homer1a in vitro.
abstract: Interactions of neurons with microglia may play a dominant role in sleep regulation. TNF may exert its somnogeneic effects by promoting attraction of microglia and their processes to the vicinity of dendrites and synapses. We found TNF to stimulate neurons (i) to produce CCL2, CCL7 and CXCL10, chemokines acting on mononuclear phagocytes and (ii) to stimulate the expression of the macrophage colony stimulating factor (M-CSF/Csf1), which leads to elongation of microglia processes. TNF may also act on neurons by affecting the expression of genes essential in sleep-wake behavior. The neuronal expression of Homer1a mRNA, increases during spontaneous and enforced periods of wakefulness. Mice with a deletion of Homer1a show a reduced wakefulness with increased non-rapid eye movement (NREM) sleep during the dark period. Recently the TNF-dependent increase of NREM sleep in the dark period of mice with CD40-induced immune activation was found to be associated with decreased expression of Homer1a. In the present study we investigated the effects of TNF and IL-1β on gene expression in cultures of the neuronal cell line HT22 and cortical neurons. TNF slightly increased the expression of Homer1a and IL-1β profoundly enhanced the expression of Early growth response 2 (Egr2). The data presented here indicate that the decreased expression of Homer1a, which was found in the dark period of mice with CD40-induced increase of NREM sleep is not due to inhibitory effects of TNF and IL-1β on the expression of Homer1a in neurons.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Maureen
authors.initials: M
authors.lastname: Karrer
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Martin Alexander
authors.initials: MA
authors.lastname: Lopez
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Meier
authors.affiliation: Center for Integrative Genomics (CIG), University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Cyril
authors.initials: C
authors.lastname: Mikhail
authors.affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Omolara O
authors.initials: OO
authors.lastname: Ogunshola
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Andreas Felix
authors.initials: AF
authors.lastname: Müller
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Strauss
authors.affiliation: Center for Integrative Genomics (CIG), University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Tafti
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland. Electronic address: fontana.adriano7@gmail.com.
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D018925:Chemokines / Q000097:blood / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D053583:Interleukin-1beta / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D018925:Chemokines; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D000072233:Homer Scaffolding Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: Depression; Inflammatory bowel disease; Multiple sclerosis; Neuroinflammation; Rheumatoid arthritis; Sickness behavior