Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis.
Synaptic plasticity in glutamatergic and GABAergic neurotransmission following chronic memantine treatment in an in vitro model of limbic epileptogenesis.
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DOI：
10.1016/j.neuropharm.2013.10.016
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发表时间：
2014-02
影响因子：
4.7
通讯作者：
Bausch SB
中科院分区：
文献类型：
--
作者：
He S;Bausch SB
用高亲和力竞争性和非竞争性拮抗剂慢性阻断N-甲基-D-天冬氨酸受体（NMDAR）可导致癫痫发作加重，可能是由于谷氨酸能和GABA能传递失衡所致。中度亲和力NMDAR拮抗剂美金刚在体内的急性给药与促惊厥和抗惊厥特性相关。长期使用美金刚胺会加重癫痫发作。因此，我们假设慢性美金刚治疗将增加多巴胺能和减少GABA能传递，类似于高亲和力竞争性和非竞争性拮抗剂。为了验证这一假设，用美金刚胺处理器官型海马切片培养物17-21天，然后进行电生理记录。从齿状颗粒细胞的全细胞记录显示，慢性美金刚治疗轻微，但显着增加sEPSC频率，mEPSC振幅和mEPSC电荷转移，符合最低限度地增加的多巴胺能传输。慢性美金刚治疗也增加了sIPSC和mIPSC的频率和振幅，表明GABA能传递增加。结果表明，一个简单的不平衡之间的谷氨酸能和γ-氨基丁酸能神经传递可能不是基础美金刚胺的igotogenic属性。也就是说，在当前研究中，对谷氨酸能和GABA能传递进行了独立测定。在电路完整的条件下，谷氨酸能和GABA能传输之间更复杂的相互作用可能占上风。
Chronic N-methyl-D-aspartate receptor (NMDAR) blockade with high affinity competitive and uncompetitive antagonists can lead to seizure exacerbation, presumably due to an imbalance in glutamatergic and GABAergic transmission. Acute administration of the moderate affinity NMDAR antagonist memantine in vivo has been associated with pro- and anticonvulsive properties. Chronic treatment with memantine can exacerbate seizures. Therefore, we hypothesized that chronic memantine treatment would increase glutamatergic and decrease GABAergic transmission, similar to high affinity competitive and uncompetitive antagonists. To test this hypothesis, organotypic hippocampal slice culture were treated for 17–21 days with memantine and then subjected to electrophysiological recordings. Whole-cell recordings from dentate granule cells revealed that chronic memantine treatment slightly, but significantly increased sEPSC frequency, mEPSC amplitude and mEPSC charge transfer, consistent with minimally increased glutamatergic transmission. Chronic memantine treatment also increased both sIPSC and mIPSC frequency and amplitude, suggestive of increased GABAergic transmission. Results suggest that a simple imbalance between glutamatergic and GABAergic neurotransmission may not underlie memantine’s ictogenic properties. That said, glutamatergic and GABAergic transmission were assayed independently of one another in the current study. More complex interactions between glutamatergic and GABAergic transmission may prevail under conditions of intact circuitry.
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影响因子：
25
作者：
Fredj, Naila Ben;Burrone, Juan
通讯作者：
Burrone, Juan
影响因子：
2.5
作者：
KORNHUBER, J;QUACK, G
通讯作者：
QUACK, G
影响因子：
2.5
作者：
Bausch, SB;McNamara, JO
通讯作者：
McNamara, JO
DOI：
10.1073/pnas.96.20.11631
发表时间：
1999-09-28
影响因子：
11.1
作者：
McKinney, RA;Lüthi, A;Thompson, SM
通讯作者：
Thompson, SM
DOI：
10.1007/978-1-60327-263-6_11
发表时间：
2009-01-01
期刊：
ANIMAL MODELS OF EPILEPSY: METHODS AND INNOVATIONS
影响因子：
--
作者：
Bausch, Suzanne B.
通讯作者：
Bausch, Suzanne B.