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Synaptic NMDAR2b Activation Leads to Abnormal CASK Expression in Erileptic Patients and in an Experimental Rat of Epilepsy

Author: ZhouYan
Tutor: WangXueFeng
School: Chongqing Medical University
Course: Neurology
Keywords: CASK epilepsy synapses lentivirus NMDAR2b
CLC: R742.1
Type: Master's thesis
Year: 2013
Downloads: 11
Quote: 0
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Abstract


Objective：To explore the expression pattern of CASK in the brains of intractabletemporal lobe epileptic patients and epileptic rat modal, and themechanism of CASK acting on epilepsy.Methods：Sample from30patients were chosen randomly from our epilepsybrain tissue bank. Using immunohistochemistry, immunoflurescence andwestern blotting, we measured the expression of CASK in the brain tissuesof these patients with intractable temporal lobe epilepsy (TLE) and thecontrols.56healthy adult male Sprague–Dawley rats were divided into8groups (n=7per group): control group and groups assessed at1d,3d,7d,14d,30d and60days after kindling by lithium chloride-pilocarpine, CASKexpression were measured again by immunohistochemistry,immunoflurescence and western blotting. A modified lentivirus was usedto knockdown CASK expression in rats. Subsequently, the behavior of these rats was observed in the first hour after kindling; and the expressionof N-methel-D-aspartate receptor subunit2b (NMDAR2b) which is thedownstream of CASK complex was further examined post-seizure.Results:The results of immunofluorescence reveal CASK is expressed onlyin neurons not gliacyte in both brains of epileptic patients and experimental rats, and the results of immunohistochemistry show CASK expression in experimental group is strong than that in control group. In thehuman sample, the western blotting bands shown CASK expression inthe temporal neocortex of TLE patients was obviously elevated than inthe controls. In the epileptic rat modal, CASK expression in the hippocampus was reduced to minimum at1d after kindling, and maintained at increased levels until60days (except at14days)(p<0.05); in thecortex CASK expression increased gradually from6h to60days immediately following kindling (p<0.05). Moreover, CASK knockdown decreased both seizure frequency and seizure class, and reduced NMDAR2b expression at different time point following kindling.Conclusions:The results show expression of CASK is abnormal in both brainsof TLE patients and experimental rats, and indicate CASK is linked toepilepsy via its action on synaptic NMDAR2b, which may be the poten tial target of anti-epileptic drugs.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Brain diseases > Epilepsy
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