Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy

被引:581
作者
Brooks-Kayal, AR
Shumate, MD
Jin, H
Rikhter, TY
Coulter, DA
机构
[1] Childrens Hosp Philadelphia, Pediat Reg Epilepsy Progam, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Joseph Stokes Res Inst, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA
[5] Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurol, Richmond, VA 23298 USA
[6] Virginia Commonwealth Univ, Med Coll Virginia, Dept Physiol & Anat, Richmond, VA 23298 USA
关键词
D O I
10.1038/2661
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Temporal robe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.
引用
收藏
页码:1166 / 1172
页数:7
相关论文
共 45 条
[1]   RELEASE OF ENDOGENOUS ZN-2+ FROM BRAIN-TISSUE DURING ACTIVITY [J].
ASSAF, SY ;
CHUNG, SH .
NATURE, 1984, 308 (5961) :734-736
[2]  
Brooks-Kayal AR, 1998, J NEUROCHEM, V70, P1017
[3]   Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model [J].
Buhl, EH ;
Otis, TS ;
Mody, I .
SCIENCE, 1996, 271 (5247) :369-373
[4]  
BUREAU M, 1990, MOL PHARMACOL, V37, P497
[5]  
Burgard EC, 1996, MOL PHARMACOL, V50, P119
[6]   Presence of mRNA for glutamic acid decarboxylase in both excitatory and inhibitory neurons [J].
Cao, YX ;
Wilcox, KS ;
Martin, CE ;
Rachinsky, TL ;
Eberwine, J ;
Dichter, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9844-9849
[7]  
DEDEYN P, 1990, ACTA NEUROL BELG, P90
[8]   Loreclezole enhances apparent desensitization of recombinant GABA(A) receptor currents [J].
Donnelly, JL ;
Macdonald, RL .
NEUROPHARMACOLOGY, 1996, 35 (9-10) :1233-1241
[9]   FUNCTIONAL AND MOLECULAR DISTINCTION BETWEEN RECOMBINANT RAT GABA-A RECEPTOR SUBTYPES BY ZN-2+ [J].
DRAGUHN, A ;
VERDORN, TA ;
EWERT, M ;
SEEBURG, PH ;
SAKMANN, B .
NEURON, 1990, 5 (06) :781-788
[10]   ANALYSIS OF GENE-EXPRESSION IN SINGLE LIVE NEURONS [J].
EBERWINE, J ;
YEH, H ;
MIYASHIRO, K ;
CAO, YX ;
NAIR, S ;
FINNELL, R ;
ZETTEL, M ;
COLEMAN, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3010-3014