title: Induction of TNF-α signaling cascade in neonatal rat brain during propofol anesthesia.
abstract: Propofol anesthesia can trigger pro- and anti-apoptotic signaling pathways in the rat brain. In our previous work, we demonstrated that propofol causes widespread apoptotic neurodegeneration in 7-postnatal-day-old (PND7) but not in PND14 rat neurons. The mechanism responsible for these opposing outcomes is unknown, apparently linked to the specific stage of brain development. The present study aims to elucidate the anti-apoptotic process that is activated in the cortex and thalamus of PND14 Wistar rats during the first 48 h after the onset of propofol anesthesia. We showed that the expression of tumor necrosis factor-α (TNF-α) and several components of its pathway, TNFR1 and caspase-8, was significantly increased in the cortex and thalamus. Nuclear factor kappa B (NF-κB) p65 was downregulated in the cortex and upregulated in the thalamus. The expression of c-Fos was upregulated only in the cortex, showing opposed profile compared to NF-κB p65. Double immunofluorescence staining revealed the colocalization of NF-κB p65 with neuronal marker (NeuN), but with predominantly cytoplasmic localization. Finally, X-linked inhibitor of apoptosis protein (XIAP) was upregulated in both examined structures. Immunohistochemical staining with Iba-1 revealed that the treatment did not induce changes in microglial morphology. Our results (i) reveal that the simultaneous activation of pro- and anti-apoptotic signaling occurs after propofol anesthesia, and (ii) pinpoint the potential neuroprotective role of XIAP in anesthesia-induced neurotoxicity.
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia; Department of Biochemistry and Goodman Cancer Research Centre, McGill University, 1160 Pine Ave. West, H3A 1A3 Montreal, QC, Canada.
authors.forename: Jelena
authors.initials: J
authors.lastname: Popić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Pešić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Desanka
authors.initials: D
authors.lastname: Milanović
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Lončarević-Vasiljković
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Kosara
authors.initials: K
authors.lastname: Smiljanić
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Selma
authors.initials: S
authors.lastname: Kanazir
authors.affiliation: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: sabir@ibiss.bg.ac.rs.
authors.forename: Sabera
authors.initials: S
authors.lastname: Ruždijić
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D006993:Hypnotics and Sedatives; D051034:Inhibitor of Apoptosis Proteins; D014409:Tumor Necrosis Factor-alpha; C494837:Xiap protein, rat; D053181:Caspase 8; D010751:Phosphopyruvate Hydratase; D015742:Propofol
keywords: Brain development; NF-κB; Propofol; TNF-α signalling; XIAP; c-Fos