SSADH deficiency leads to elevated extracellular GABA levels and increased GABAergic neurotransmission in the mouse cerebral cortex.
SSADH deficiency leads to elevated extracellular GABA levels and increased GABAergic neurotransmission in the mouse cerebral cortex.
复制标题
DOI：
10.1007/s10545-008-0941-7
复制
发表时间：
2008-12
影响因子：
4.2
通讯作者：
Jensen, K.
中科院分区：
文献类型：
--
作者：
Drasbek, K. R.;Vardya, I.;Delenclos, M.;Gibson, K. M.;Jensen, K.
琥珀酸半醛脱氢酶缺乏症是一种遗传性疾病，患者表现为神经发育迟缓、共济失调和癫痫发作。最近设计的SSADH基因敲除(KO)小鼠模拟了人类疾病的严重形式。SSADH酶参与了抑制性神经递质GABA的分解，研究表明，这些小鼠大脑中GABA增加，大脑皮层GABA受体β2亚单位下调。在这里，我们使用脑片电生理学来研究SSADHKO小鼠皮质GABA神经递质的变化。在第2/3层锥体细胞，反映GABA能突触接触活动的自发抑制性突触后电流(IPSCs)在SSADHKO小鼠中是正常的。KO小鼠单轴突电刺激诱发的IPSCs也是正常的。相反，由推测的突触外GABAA受体介导的紧张性抑制强烈增加，表明细胞外GABA水平显著升高。皮质GABA能神经递质的过度传递可能参与了SSADH虚证的惊厥活动。
Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inherited disorder in which patients display neurodevelopmental retardation, ataxia, and epileptic seizures. The recently engineered SSADH knock-out (KO) mouse models the severe form of the human disorder. The SSADH enzyme participates in the breakdown of the inhibitory neuro-transmitter GABA, and studies have shown increases in brain GABA and downregulation of GABAA receptor β2 subunits in the cerebral cortex of these mice. Here, we used brain slice electrophysiology to investigate the alterations in GABA neurotransmission in SSADH KO mouse cortex. In layer 2/3 pyramidal cells, spontaneous inhibitory postsynaptic currents (IPSCs), reflecting activity of GABAergic synaptic contacts, were normal in SSADH KO mice. Also, IPSCs evoked by electrical single-axon stimulation in KO mice were normal. In contrast, tonic inhibition mediated by presumed extrasynaptic GABAA receptors was strongly increased, indicating significantly raised extracellular GABA levels. The excessive cortical GABAergic neurotransmission may participate in the seizure activity in SSADH deficiency.
登录
查看更多内容
影响因子：
5.5
作者：
Rivera, C;Voipio, J;Kaila, K
通讯作者：
Kaila, K
影响因子：
3.7
作者：
Jensen, K;Mody, I
通讯作者：
Mody, I
影响因子：
5.3
作者：
Chiu, CS;Brickley, S;Lester, HA
通讯作者：
Lester, HA
影响因子：
30.8
作者：
Hogema, BM;Gupta, M;Gibson, KM
通讯作者：
Gibson, KM
影响因子：
4.8
作者：
Mann, Edward O.;Mody, Istvan
通讯作者：
Mody, Istvan