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01-11-2018 | Original Article

Expression analysis of GRIN2B, BDNF, and IL-1β genes in the whole blood of epileptic patients

Authors: Anoushe Zhand, Arezou Sayad, Soudeh Ghafouri-Fard, Shahram Arsang-Jang, Mehrdokht Mazdeh, Mohammad Taheri

Published in: Neurological Sciences | Issue 11/2018

Abstract

Epilepsy is a brain disorder with a global prevalence of 1%. It has been attributed to genetics and environmental factors. Despite efforts to identify the molecular pathology of epilepsy, the underlying mechanism is not understood yet. This study was carried out to compare GRIN2B, BDNF, and IL-1β gene expressions in 50 patients suffering from generalized epilepsy with tonic-colonic seizures and 50 age- and sex-matched healthy subjects using TaqMan Real-time PCR. Our results demonstrated significant upregulation of these genes in people with epilepsy compared with healthy subjects. We also found a positive correlation between GRIN2B and BDNF expression (r²=0.4619, p < 0.0001), BDNF and IL-1β expression (r² = 0.515, p < 0.0001), and GRIN2B and IL-1β gene expressions (r² = 0.666, p < 0.0001) which implies the possibility to estimate the expression level of these genes by assessment of expression of one of them. Considering the results of the previous animal studies which showed upregulation of these genes in brain tissues of epileptic animals, the expression levels of GRIN2B, BDNF, and IL-1β in blood samples might be related to their expression in brain samples. Future studies are needed to assess the role of these genes in the pathogenesis of epilepsy and evaluate whether altered expression of these genes along with imaging methods can facilitate subtyping the epilepsy.

Ghasemi M, Schachter SC (2011) The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav 22(4):617–640CrossRef

Binder DK, Scharfman HE (2004) Mini review. Growth Factors 22(3):123–131CrossRef

Binder DK, Croll SD, Gall CM, Scharfman HE (2001) BDNF and epilepsy: too much of a good thing? Trends Neurosci 24(1):47–53CrossRef

Vezzani A, Baram TZ (2007) New roles for interleukin-1 beta in the mechanisms of epilepsy. Epilepsy Curr 7(2):45–50CrossRef

Araujo DM, Cotman CW (1995) Differential effects of interleukin-1β and interleukin-2 on glia and hippocampal neurons in culture. Int J Dev Neurosci 13(3):201–212CrossRef

Lin S-Y, Wu K, Levine ES, Mount HT, Suen P-C, Black IB (1998) BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities. Mol Brain Res 55(1):20–27CrossRef

Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410(6831):988–994CrossRef

Caldeira MV, Melo CV, Pereira DB, Carvalho RF, Carvalho AL, Duarte CB (2007) BDNF regulates the expression and traffic of NMDA receptors in cultured hippocampal neurons. Mol Cell Neurosci 35(2):208–219CrossRef

Miller AH, Haroon E, Raison CL, Felger JC (2013) Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety 30(4):297–306CrossRef

10.

Hu S, Sheng WS, Ehrlich LC, Peterson PK, Chao CC (2000) Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation 7(3):153–159CrossRef

11.

Mazdeh M, Komaki A, Omrani MD, Gharzi V, Sayad A, Taheri M, Ghafouri-Fard S (2018) Expression analysis of beta-secretase 1 (BACE1) and its naturally occurring antisense (BACE1-AS) in blood of epileptic patients. Neurol Sci: Off J Italian Neurol Soc Italian Soc Clin NeurophysiolCrossRef

12.

Mazdeh M, Ghafouri-Fard S, Hatami M, Eftekharian MM, Ganji M, Sayad A, Arsang-Jang S, Taheri M, Omrani MD (2018) Expression analysis of vitamin D signaling pathway genes in epileptic patients. J Mol Neurosci: MN 64(4):551–558CrossRef

13.

Liew C-C, Ma J, Tang H-C, Zheng R, Dempsey AA (2006) The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 147(3):126–132CrossRef

14.

Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46(11):1724–1743CrossRef

15.

Mathern GW, Pretorius JK, Kornblum HI, Mendoza D, Lozada A, Leite JP et al (1997) Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients. Brain 120(11):1937–1959CrossRef

16.

Mathern GW, Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Mendoza D, Fried I, Sakamoto AC, Assirati JA, Adelson PD, Peacock WJ (1996) Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining. Neuroreport 7(5):1029–1035CrossRef

17.

Franck JE, Pokorny J, Kunkel DD, Schwartzkroin PA (1995) Physiologic and morphologic characteristics of granule cell circuitry in human epileptic hippocampus. Epilepsia 36(6):543–558CrossRef

18.

Isokawa M, Levesque MF (1991) Increased NMDA responses and dendritic degeneration in human epileptic hippocampal neurons in slices. Neurosci Lett 132(2):212–216CrossRef

19.

Masukawa LM, Higashima M, Hart GJ, Spencer DD, O’Connor MJ (1991) NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients. Brain Res 562(1):176–180CrossRef

20.

Kiessling M, Gass P (1993) Immediate early gene expression in experimental epilepsy. Brain Pathol 3(4):381–393CrossRef

21.

Morgan JI, Curran T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 14(1):421–451CrossRef

22.

Gall CM (1993) Seizure-induced changes in neurotrophin expression: implications for epilepsy. Exp Neurol 124(1):150–166CrossRef

23.

Isackson PJ, Huntsman MM, Murray KD, Gall CM (1991) BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron 6(6):937–948CrossRef

24.

Ernfors P, Bengzon J, Kokaia Z, Persson H, Lindvall O (1991) Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron 7(1):165–176CrossRef

25.

Lindvall O, Kokaia Z, Bengzon J, Elme E, Kokaia M (1994) Neurotrophins and brain insults. Trends Neurosci 17(11):490–496CrossRef

26.

Conner JM, Lauterborn JC, Yan Q, Gall CM, Varon S (1997) Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. J Neurosci 17(7):2295–2313CrossRef

27.

Yan Q, Rosenfeld R, Matheson C, Hawkins N, Lopez O, Bennett L et al (1997) Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system. Neuroscience 78(2):431–448CrossRef

28.

Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14(3):347–353CrossRef

29.

Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 37(12):1553–1561CrossRef

30.

Poduslo JF, Curran GL (1996) Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3. BDNF Mol Brain Res 36(2):280–286CrossRef

31.

Youn Y, Sung IK, Lee IG (2013) The role of cytokines in seizures: interleukin (IL)-1β, IL-1Ra, IL-8, and IL-10. Korean J Pediatr 56(7):271–274CrossRef

32.

Ferrari CC, Depino AM, Prada F, Muraro N, Campbell S, Podhajcer O, Perry VH, Anthony DC, Pitossi FJ (2004) Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. Am J Pathol 165(5):1827–1837CrossRef

33.

Allan SM, Tyrrell PJ, Rothwell NJ (2005) Interleukin-1 and neuronal injury. Nat Rev Immunol 5(8):629–640CrossRef

34.

Nguyen MD, Julien J-P, Rivest S (2002) Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3(3):216–227CrossRef

35.

Tian G-F, Azmi H, Takano T, Xu Q, Peng W, Lin J, Oberheim NA, Lou N, Wang X, Zielke HR, Kang J, Nedergaard M (2005) An astrocytic basis of epilepsy. Nat Med 11(9):973–981CrossRef

36.

Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, Friedman A (2004) Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24(36):7829–7836CrossRef

37.

Van Vliet E, da Costa AS, Redeker S, Van Schaik R, Aronica E, Gorter J (2007) Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130(2):521–534CrossRef

38.

Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens M, Bartfai T et al (2003) Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 23(25):8692–8700CrossRef

39.

Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E et al (2001) CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity. Nat Neurosci 4(7):702–710CrossRef

40.

Namekata K, Harada C, Kohyama K, Matsumoto Y, Harada T (2008) Interleukin-1 stimulates glutamate uptake in glial cells by accelerating membrane trafficking of Na+/K+-ATPase via actin depolymerization. Mol Cell Biol 28(10):3273–3280CrossRef

41.

Mairuae N, Cheepsunthorn P (2018) Valproic acid attenuates nitric oxide and interleukin-1β production in lipopolysaccharide-stimulated iron-rich microglia. Biomed Rep 8(4):359–364PubMedPubMedCentral

42.

Croce N, Mathe AA, Gelfo F, Caltagirone C, Bernardini S, Angelucci F (2014) Effects of lithium and valproic acid on BDNF protein and gene expression in an in vitro human neuron-like model of degeneration. J Psychopharmacol(Oxford, England) 28(10):964–972CrossRef

43.

Liu Y, Beyer A, Aebersold R (2016) On the dependency of cellular protein levels on mRNA abundance. Cell 165(3):535–550CrossRef

Title: Expression analysis of GRIN2B, BDNF, and IL-1β genes in the whole blood of epileptic patients
Authors: Anoushe Zhand
Arezou Sayad
Soudeh Ghafouri-Fard
Shahram Arsang-Jang
Mehrdokht Mazdeh
Mohammad Taheri
Publication date: 01-11-2018
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 11/2018
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-018-3533-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression analysis of GRIN2B, BDNF, and IL-1β genes in the whole blood of epileptic patients

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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