Expression and distribution of GAD-65/67 in 23 patients with epileptogenic forcal cortical dysplasia
RAO Ying-hua1 ZHANG Xun1 QIN Ming-jun1 HU Bin2
1.Department of Neurosurgery,the Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital),Guangdong Province,Guangzhou 510370,China;
2.Department of Neurosurgery,the Affiliated Second Hospital of Guangzhou Medical University,Guangdong Province,Guangzhou 510500,China
Abstract:Objective To explore the expression and distribution of GAD-65/67 in patients with forcal cortical dysplasia(FCD)epilepsy.Methods Surgical focus specimen of inpatients were collected from the Affiliated Brain Hospital of Guangzhou Medical University and the Affiliated Second Hospital of Guangzhou Medical University from October 2017 to October 2019.The expression of GAD-65/67 was observed by immunohistochemical staining in 23 patients with FCD epilepsy who underwent surgical resection (the experimental group)and 7 normal brain tissues without epilepsy(the control group).All the stained sections were examined under a microscope and photographed with a digital camera and the image chromatic aberration was analyzed by IEE 7.0 software.Results The expression of GAD-65/67 was found in both the experimental group and the control group.In the control group,GAD-65/67 was found to be evenly distributed in nerve fibers and synapses in brain tissue.In the experimental group,abnormal morphology and arrangement of neurons were observed and the expression and distribution of GAD-65/67 were changed correspondingly.Conclusion This study suggests that the abnormal distribution of GAD-65/67 may be attributed to the abnormal development of cerebral cortex in FCD,resulting in the decrease of GABA inhibition.
Roland DT,Rainer S,Terence JO,et al.Epilepsy in Adults[J].JLancet,2019,393(10 172):689-701.
[2]
Carmen B,Judith HC,Kees B,et al.Trends in pediatric epilepsy surgery in Europe between 2008 and 2015:country-,center-,and age-specific variation[J].Epilepsia,2020,61(2):216-227
[3]
Liu YH,Vasily G,Bardakjian BL,et al.Excitation and Inhibition Balance Underlying Epileptiform Activity[J].IEEETrans Biomed Eng,2020,1:1-12
[4]
Kenneth NF,Brad R,David A.Laminar distribution of subsets of GABA ergic axon terminals in human prefrontal cortex[J].Front Neuroanat,2018,12(9):1-12.
[5]
Shi YW,Zhang Q,Cai K,et al.Synaptic clustering differences due to different GABRB3 mutat ions cause variable epilepsy syndromes[J].Brain,2019,142(10):3028-3044.
[6]
Dai-Hung N,Thanh S.An updated review on pharmaceutical properties of gamma-aminob utyric acid[J].Molecules,2019,24(15):2678-2701.
[7]
Blumcke I,Thom M,Aronica E,et al.The clinicopathologic spectrum of focal cortical dysplasias:a co-nsensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission[J].Epilepsia,2011,52(1):158-174.
[8]
Taylor DC,Falconer MA,Bruton CJ,et al.Focal dysplasia ofthe cerebral cortex in epilepsy[J].JNeurol Neurosurg Psychiatry,1971,34(4):369-387.
[9]
Yan Y,Xie G,Zhou H,et al.Altered spontaneous brain activity in patients with childhood absence epilepsy:associations with treatment Effects[J].Neuroreport,2020,31(8):613-618.
[10]
Harald S,Ivan M,Nina M,et al.Alterations in GABAA receptor subunit expression in the amygdala and entorhinal cortex in human temporal lobe epilepsy[J].J Neuropathol Exp Neurol,2019,78(11):1022-1048.
[11]
Harald S,Ivan M,Nina M,et al.GABA A receptor subunits in the human amygdala and hippocampus:immunohistochemical distribution of 7 subunits[J].JComp Neurol,2018,526(2):324-348.
[12]
Sheila MSS,James AH,Sandra JH,et al.Decreased epileptogenesis in mice lac king the system xc-transporter occurs in association with a reduction in AMPA receptor subunit gluA1[J].Epilepsia Open,2019,4(1):133-143.
[13]
Calcagnotto ME,Paredes MF,Tihan T,et al.Dysfunction of synaptic inhibitionin epilepsy associated with focal cortical dysplasia[J].JNeurosci,2005,25(42):9649-9657.
[14]
Seong EL,Yunjong L,Gum HL.The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain[J].Arch Pharm Res,2019,42(12):1031-1039.
[15]
Trung NL,Zhou QP,Inma C,et al.GABAergic interneuron differentiation in the basal forebrain is mediated through direct regulation of glutamic acid decarboxylase isoforms by dlx home box transcription factors[J].JNeurosci,2017,37(36):8816-8829.
[16]
Walls AB,Eyjolfsson EM,Smeland OB,et al.Knockout of GAD65 has major impact on synaptic GABA synthesized from astrocyte-derived glutamine[J].J Cereb Blood Flow Metab,2011,31(2):494-503.
[17]
Esclapez M,Houser CR.Up-regulation of GAD65 and GAD67 in remaining hippoampal GABA neurons in a model of temporal lobe epilepsy[J].JComp Neurol,1999,412(3):488-505.
[18]
Medici V,Rossini L,Deleo F,et al.Different Parvalbumin and GABA Expression Inhuman Epileptogenic Focal Cortical Dysplasia[J].Epilepsia,2016,57(7):1109-1119.
[19]
Garbelli R,Meroni A,Magnaghi G,et al.Architectural(type IA)focal cortical dysplasia and parvalbum in immunostaining in temporal lobe epilepsy[J].Epilepsia,2006,47(6):1074-1078.
[20]
Guerrini R,Duchowny M,Jayakar P,et al.Diagnostic methods and treatment options for focal cortical dysplasia[J].Epilepsia,2015,56(11):1669-1686.
[21]
D′Antuono M,Louvel J,Kohling R,et al.GABA a receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex[J].Brain,2004,127(Pt 7):1626-1640
[22]
Vincent M,Jonathan C,Andreas L,et al.KCC2 overexpression prevents the paradoxical seizure-promoting action of somatic inhibition[J].Nat Commun,2019,15,10(1):1225-1238.
[23]
Krsek P,Maton B,Korman B,et al.Different features of histopathological subtypes of pediatric focal cortical dysplasia[J].Ann Neurol,2008,63(6):758-769.
[24]
Tim JV,Banu S,Cyrille HF,et al.Long-term seizure outcome after epilepsy surgery in patients with mild malformation of cortical development and focal cortical dysplasia[J].Epilepsia Open,2019,4(1):170-175.