Pathophysiological power of improper tonic GABA(A) conductances in mature and immature models.
Pathophysiological power of improper tonic GABA(A) conductances in mature and immature models.
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DOI：
10.3389/fncir.2013.00170
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发表时间：
2013
影响因子：
3.5
通讯作者：
Fukuda A
中科院分区：
文献类型：
--
作者：
Egawa K;Fukuda A
High-affinity extrasynaptic gamma-aminobutyric acid A (GABAA) receptors are tonically activated by low and consistent levels of ambient GABA, mediating chronic inhibition against neuronal excitability (tonic inhibition) and the modulation of neural development. Synaptic (phasic) inhibition is spatially and temporally precise compared with tonic inhibition, which provides blunt yet strong integral inhibitory force by shunting electrical signaling. Although effects of acute modification of tonic inhibition are known, its pathophysiological significance remains unclear because homeostatic regulation of neuronal excitability can compensate for long-term deficit of extrasynaptic GABAA receptor activation. Nevertheless, tonic inhibition is of great interest for its pathophysiological involvement in central nervous system (CNS) diseases and thus as a therapeutic target. Together with the development of experimental models for various pathological states, recent evidence demonstrates such pathological involvements of tonic inhibition in neuronal dysfunction. This review focuses on the recent progress of tonic activation of GABAA conductance on the development and pathology of the CNS. Findings indicate that neuronal function in various brain regions are exacerbated with a gain or loss of function of tonic inhibition by GABA spillover. Disturbance of tonic GABAA conductance mediated by non-synaptic ambient GABA may result in brain mal-development. Therefore, various pathological states (epilepsy, motor dysfunctions, psychiatric disorders, and neurodevelopmental disorders) may be partly attributable to abnormal tonic GABAA conductances. Thus, the tone of tonic conductance and level of ambient GABA may be precisely tuned to maintain the regular function and development of the CNS. Therefore, receptor expression and factors for regulating the ambient GABA concentration are highlighted to gain a deeper understanding of pathology and therapeutic strategy for CNS diseases.
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DOI：
10.1177/0269881111405366
发表时间：
2011-08
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Braudeau J;Delatour B;Duchon A;Pereira PL;Dauphinot L;de Chaumont F;Olivo-Marin JC;Dodd RH;Hérault Y;Potier MC
通讯作者：
Potier MC
影响因子：
2.3
作者：
Aoki, Chiye;Sabaliauskas, Nicole;Chowdhury, Tara;Min, Jung-Yun;Colacino, Anna Rita;Laurino, Kevin;Barbarich-Marsteller, Nicole C.
通讯作者：
Barbarich-Marsteller, Nicole C.
影响因子：
4.7
作者：
Atack, John R.;Bayley, Peter J.;Dawson, Gerard R.
通讯作者：
Dawson, Gerard R.
影响因子：
2.5
作者：
Belichenko, Pavel V.;Klescrevnikov, Alexander M.;Mobley, William C.
通讯作者：
Mobley, William C.
影响因子：
64.8
作者：
Andang, Michael;Hjerling-Leffler, Jens;Ernfors, Patrik
通讯作者：
Ernfors, Patrik