研究人員第一次在動物模型中，抑制了發(fā)生于腦部的癲癇,。他們利用基因療法修改腦部的信號路徑,，發(fā)現(xiàn)可以顯著地減少大鼠的癲癇癥發(fā)作。
這項研究是由賓州大學(xué)醫(yī)學(xué)院小兒科神經(jīng)學(xué)家Amy R. Brooks-Kayal所引導(dǎo),。他表示,，這項研究提供了一個概念,，證明可經(jīng)由修改腦部神經(jīng)細(xì)胞中的特殊信號路徑，來治療癲癇癥,。這項研究結(jié)果發(fā)表于11月1 日的Journal of Neuroscience中,。
研究人員進行治療的腦部區(qū)域稱為齒狀回（dentate gyrus），他們把焦點集中于一種gamma-aminobutyric acid (GABA)A型受體,。當(dāng)GABA(A)受體被活化后,，可抑制腦細(xì)胞反復(fù)過度的刺激所引發(fā)的癲癇。
癲癇是由于刺激神經(jīng)元的二種神經(jīng)傳導(dǎo)物質(zhì)：谷胺酸與GABA系統(tǒng)的不平衡所致,。GABA所扮演的抑制角色在齒狀回中是特別重要的,，因為齒狀回是腦部的活動進入海馬回的門戶，而海馬回是引起最常見的兒童和成人癲癇類型：顳葉癲癇之部位,。GABA(A)受體含有五個次單位,，研究人員之前在動物研究中，發(fā)現(xiàn)有癲癇的大鼠之a(chǎn)lpha1次單位含量偏低且alpha4 次單位含量偏高,。
所以,，研究人員傳輸基因以修改alpha1 次單位的表現(xiàn)，結(jié)果發(fā)現(xiàn)可以使alpha1 蛋白質(zhì)的量增加,，而使癲癇的發(fā)生率減少了三倍,。雖然這只是一項短期研究，無法預(yù)測長期的結(jié)果,，但卻有助于引導(dǎo)出治療癲癇的基因療法,。
部分英文原文：
Enhancing GABAA Receptor 1 Subunit Levels in Hippocampal Dentate Gyrus Inhibits Epilepsy Development in an Animal Model of Temporal Lobe Epilepsy.
Differential expression of GABA(A) receptor (GABR) subunits has been demonstrated in hippocampus from patients and animals with temporal lobe epilepsy (TLE), but whether these changes are important for epileptogenesis remains unknown. Previous studies in the adult rat pilocarpine model of TLE found reduced expression of GABR alpha1 subunits and increased expression of alpha4 subunits in dentate gyrus (DG) of epileptic rats compared with controls. To investigate whether this altered subunit expression is a critical determinant of spontaneous seizure development, we used adeno-associated virus type 2 containing the alpha4 subunit gene (GABRA4) promoter to drive transgene expression in DG after status epilepticus (SE). This novel use of a condition-dependent promoter upregulated after SE successfully increased expression of GABR alpha1 subunit mRNA and protein in DG at 1-2 weeks after SE. Enhanced alpha1 expression in DG resulted in a threefold increase in mean seizure-free time after SE and a 60% decrease in the number of rats developing epilepsy (recurrent spontaneous seizures) in the first 4 weeks after SE. These findings provide the first direct evidence that altering GABR subunit expression can affect the development of epilepsy and suggest that alpha1 subunit levels are important determinants of inhibitory function in hippocampus.
