Hippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients

dc.creatorTeocchi, MA
dc.creatorFerreira, AED
dc.creatorde Oliveira, EPD
dc.creatorTedeschi, H
dc.creatorD'Souza-Li, L
dc.date2013
dc.dateMAY 1
dc.date2014-08-01T18:30:56Z
dc.date2015-11-26T17:54:23Z
dc.date2014-08-01T18:30:56Z
dc.date2015-11-26T17:54:23Z
dc.date.accessioned2018-03-29T00:38:02Z
dc.date.available2018-03-29T00:38:02Z
dc.identifierJournal Of Neuroinflammation. Biomed Central Ltd, v. 10, 2013.
dc.identifier1742-2094
dc.identifierWOS:000318852800001
dc.identifier10.1186/1742-2094-10-53
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/80027
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/80027
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1290779
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionBackground: Previous research in animal seizure models indicates that the pleiotropic cytokine TNF is an important effector/mediator of neuroinflammation and cell death. Recently, it has been demonstrated that TNF downregulates Klotho (KL) through the nuclear factor kappa B (NFkB) system in animal models of chronic kidney disease and colitis. KL function in the brain is unclear, although Klotho knockout (Kl(-/-)) mice exhibit neural degeneration and a reduction of hippocampal synapses. Our aim was to verify if the triad KL-NFKB1-TNF is also dysregulated in temporal lobe epilepsy associated with hippocampal sclerosis (TLE(HS)) patients. Findings: We evaluated TNF, NFKB1 and KL relative mRNA expression levels by reverse transcription quantitative PCR (RT-qPCR) in resected hippocampal tissue samples from 14 TLE(HS) patients and compared them to five post mortem controls. Four reference genes were used: GAPDH, HPRT1, ENO2 and TBP. We found that TNF expression was dramatically upregulated in TLE(HS) patients (P <0.005). NFKB1 expression was also increased (P <0.03) while KL was significantly downregulated (P <0.03) in TLE(HS) patients. Hippocampal KL expression had an inverse correlation with NFKB1 and TNF. Conclusions: Our data suggest that, similar to other inflammatory diseases, TNF downregulates KL through NFkB in TLE(HS) patients. The remarkable TNF upregulation in patients is a strong indication of hippocampal chronic inflammation. Our finding of hippocampal KL downregulation has wide implications not only for TLE(HS) but also for other neuronal disorders related to neurodegeneration associated with inflammation.
dc.description10
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFAPESP [05/565778-4]
dc.languageen
dc.publisherBiomed Central Ltd
dc.publisherLondon
dc.publisherInglaterra
dc.relationJournal Of Neuroinflammation
dc.relationJ. Neuroinflamm.
dc.rightsaberto
dc.sourceWeb of Science
dc.subjectSeizures
dc.subjectHippocampal sclerosis
dc.subjectNeuroinflammation
dc.subjectTNF
dc.subjectKL
dc.subjectNFKB1
dc.subjectGFAP
dc.subjectReference genes
dc.subjectCalcium homeostasis
dc.subjectTnf-alpha
dc.subjectInflammatory Cytokines
dc.subjectBrain
dc.subjectCalcium
dc.subjectMechanisms
dc.subjectProtein
dc.subjectMice
dc.titleHippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients
dc.typeArtículos de revistas


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