title: Hippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
authors: Laboratory of Pediatric Endocrinology, Center for Investigation in Pediatrics, University of Campinas, PO Box 6111, Campinas, SP 13083-970, Brazil.
authors: Marcelo Ananias
authors: MA
authors: Teocchi
authors: Ana Érika Dias
authors: AÉ
authors: Ferreira
authors: Evandro Pinto
authors: EP
authors: da Luz de Oliveira
authors: Helder
authors: H
authors: Tedeschi
authors: Lília
authors: L
authors: D'Souza-Li
mesh_terms: D000328:Adult; D000679:Amygdala / Q000601:surgery; D002118:Calcium / Q000378:metabolism; D002648:Child; D003627:Data Interpretation, Statistical; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism* / Q000601:surgery; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis*; D019635:Neurosurgical Procedures; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium
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