Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission
Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission
复制标题
DOI：
10.1111/j.1528-1167.2010.02756.x
复制
发表时间：
2011-01-01
期刊：
影响因子：
5.6
通讯作者：
Capogna, Marco
中科院分区：
文献类型：
--
作者：
Lalic, Tatjana;Pettingill, Philippa;Capogna, Marco
目的：边缘系统脑炎（LE）是一种以亚急性发作的记忆丧失和癫痫发作为特征的中枢神经系统疾病。一种公认的LE形式与患者血清中的电压门控钾通道复合物抗体（VGKC-Ab）相关。我们的目的是测试的假设，纯化的免疫球蛋白G（IgG）从VGKC-Ab LE血清将兴奋海马CA3锥体细胞减少VGKC功能在苔藓纤维（MF）-CA3锥体细胞synapses.Methods：我们比较了LE和健康对照IgG的影响，全细胞膜片钳和细胞外记录从CA3锥体细胞的大鼠海马急性slice.Results：我们发现，LE IgG诱导癫痫样活动在人口水平上，因为突触刺激引起多个人口的尖峰细胞外记录在CA3区。此外，LE IgG增加紧张性放电的频率，并加强MF诱发的突触反应。诱发兴奋性突触后电流（EPSC）的突触失败是显着较低的LE IgG相比，对照IgG的存在。这表明与对照IgG相比，LE IgG增加了MF-CA 3锥体细胞突触上的释放概率。有趣的是，α-dendrotoxin（120 nm），选择性Kv1.1，1.2，和1.6亚基拮抗剂VGKC，模仿LE IgG介导的effects.Conclusions：这是第一个功能证明，LE IgG降低VGKC功能在中枢神经系统突触和增加细胞兴奋性。
P>Purpose:Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses.Methods:We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices.Results:We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, alpha-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects.Conclusions:This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability.