Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients

被引：32

作者：

Wickham, Jenny ^{[1
]}

Ledri, Marco ^{[1
]}

Bengzon, Johan ^{[2
]}

Jespersen, Bo ^{[3
]}

Pinborg, Lars H. ^{[4
,5
]}

Englund, Elisabet ^{[6
]}

Woldbye, David P. D. ^{[7
]}

Andersson, My ^{[1
]}

Kokaia, Merab ^{[1
]}

机构：

[1] Lund Univ, Lund Univ Hosp, Epilepsy Ctr, Dept Clin Sci, SE-22362 Lund, Sweden

[2] Lund Univ, Skanes Univ Sjukhus, Dept Clin Sci, Neurosurg, SE-22362 Lund, Sweden

[3] Univ Copenhagen, Copenhagen Univ Hosp, Rigshosp, Dept Neurosurg, DK-2100 Copenhagen, Denmark

[4] Copenhagen Univ Hosp, Rigshosp, Dept Neurol, Bldg 6931,Blegdamsvej 9, DK-2100 Copenhagen, Denmark

[5] Copenhagen Univ Hosp, Rigshosp, Neurobiol Res Unit, Bldg 6931,Blegdamsvej 9, DK-2100 Copenhagen, Denmark

[6] Lund Univ, Dept Clin Sci, Div Oncol & Pathol, SE-22362 Lund, Sweden

[7] Univ Copenhagen, Dept Neurosci, Lab Neuropsychiat, DK-2100 Copenhagen, Denmark

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

瑞典研究理事会;

关键词：

HIPPOCAMPAL SLICES; GENE-THERAPY; SYNAPTIC-TRANSMISSION; ANTIEPILEPTIC ACTIONS; Y-2; RECEPTORS; LIMBIC SYSTEM; DENTATE GYRUS; SEIZURE; OVEREXPRESSION; MODEL;

D O I：

10.1038/s41598-019-56062-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.

引用

页数：11

共 40 条

[1] 2 DIFFERENT RESPONSES OF HIPPOCAMPAL PYRAMIDAL CELLS TO APPLICATION OF GAMMA-AMINO BUTYRIC-ACID [J].