The GABAA receptor:: a novel target for treatment of fragile X?

被引:126
作者
D'Hulst, Charlotte [1 ]
Kooy, R. Frank [1 ]
机构
[1] Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium
关键词
D O I
10.1016/j.tins.2007.06.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
GABA(A) receptors are the major inhibitory neurotransmitter receptors in the mammalian brain, implicated in anxiety, depression, epilepsy, insomnia, and learning and memory. Here, we present several lines of evidence for involvement of the GABAergic system, and in particular the GABAA receptor-mediated function, in fragile X syndrome, the most common form of inherited mental retardation. We argue that an altered expression of the GABAA receptor has neurophysiologic and functional consequences that might relate to the behavioural and neurological phenotype associated with fragile X syndrome. Interestingly, some neuropsychiatric disorders, such as anxiety, epilepsy and sleep disorders, are effectively treated with therapeutic agents that act on the GABAA receptor. Therefore, the GABAA receptor might be a novel therapeutic target for fragile X syndrome.
引用
收藏
页码:425 / 431
页数:7
相关论文
共 75 条
[11]   Fragile X mice develop sensory hyperreactivity to auditory stimuli [J].
Chen, L ;
Toth, M .
NEUROSCIENCE, 2001, 103 (04) :1043-1050
[12]   Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits [J].
Comery, TA ;
Harris, JB ;
Willems, PJ ;
Oostra, BA ;
Irwin, SA ;
Weiler, IJ ;
Greenough, WT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5401-5404
[13]   Attention and language in fragile X [J].
Cornish, K ;
Sudhalter, V ;
Turk, J .
MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS, 2004, 10 (01) :11-16
[14]   Involvement of cholinergic and GABAergic systems in the fragile X knockout mice [J].
D'Antuono, M ;
Merlo, D ;
Avoli, M .
NEUROSCIENCE, 2003, 119 (01) :9-13
[15]   Decreased expression of the GABAA receptor in fragile X syndrome [J].
D'Hulst, Charlotte ;
De Geest, Natalie ;
Reeve, Simon P. ;
Van Dam, Debby ;
De Deyn, Peter P. ;
Hassan, Bassem A. ;
Kooy, R. Frank .
BRAIN RESEARCH, 2006, 1121 :238-245
[16]   Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function [J].
Darnell, JC ;
Jensen, KB ;
Jin, P ;
Brown, V ;
Warren, ST ;
Darnell, RB .
CELL, 2001, 107 (04) :489-499
[17]  
DeLorey TM, 1998, J NEUROSCI, V18, P8505
[18]   Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest [J].
Dockendorff, TC ;
Su, HS ;
McBride, SMJ ;
Yang, ZH ;
Choi, CH ;
Siwicki, KK ;
Sehgal, A ;
Jongens, TA .
NEURON, 2002, 34 (06) :973-984
[19]   Decreased GABAA receptor expression in the seizure-prone fragile X mouse [J].
El Idrissi, A ;
Ding, XH ;
Scalia, J ;
Trenkner, E ;
Brown, WT ;
Dobkin, C .
NEUROSCIENCE LETTERS, 2005, 377 (03) :141-146
[20]   Sleep in subjects with autistic disorder: a neurophysiological and psychological study [J].
Elia, M ;
Ferri, R ;
Musumeci, SA ;
Del Gracco, S ;
Bottitta, M ;
Scuderi, C ;
Miano, G ;
Panerai, S ;
Bertrand, T ;
Grubar, JC .
BRAIN & DEVELOPMENT, 2000, 22 (02) :88-92