Structural and functional abnormalities in thalamic neurons following neocortical focal status epilepticus.
Structural and functional abnormalities in thalamic neurons following neocortical focal status epilepticus.
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DOI：
10.1016/j.nbd.2022.105934
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发表时间：
2023-01
影响因子：
6.1
通讯作者：
David, Prince
中科院分区：
文献类型：
--
作者：
Maria-Belen, Perez -Ramirez;Isabel, Parada;David, Prince
关键词：
癫痫持续状态 (SE) 是一种危及生命的紧急情况，可能导致癫痫重新发展或恶化。我们测试了这样的假设：新皮质局灶性癫痫持续状态（FSE）期间异常的皮质输出会引起丘脑的结构和功能变化，这可能导致丘脑皮质回路的过度兴奋。我们通过单侧硬膜外向麻醉小鼠的体感皮层施用惊厥药物来诱导新皮质 FSE。由此产生的局灶性脑电图发作与行为性癫痫发作相关，包括对侧局灶性肌阵挛活动，并持续 2-3 小时。 10 天和 30 天后，对大脑进行免疫组织化学 (IHC) 或体外切片记录处理。使用来自丘脑网状核中心（nRT，参见方法）、腹侧后外侧核（VPL）和来自腹基底核（VB）的腹侧后内侧核（VPM）的切片来测量NeuN免疫反应性神经元、GFAP反应性星形胶质细胞的密度以及VGLUT1 + PSD95-和VGLUT2 + PSD95-IR的共定位区域（推定）皮质和丘脑起源的兴奋性突触。全细胞电压钳记录用于测量这些细胞核中的自发 EPSC 频率。我们发现 nRT 没有显示神经元数量减少或反应性星形胶质细胞增生的证据。相反，VB 中 GFAP-IR 增加，NeuN 阳性细胞的神经元计数减少。 VB 中 VGLUT1-PSD95 和 VGLUT2-PSD95 的双重 IHC 显示兴奋性突触数量增加，可能是丘脑和皮质起源的。 nRT 和 VB 神经元中 sEPSC 的频率增加，但幅度没有增加。之前的报告表明，长时间的新皮质癫痫发作可能会导致下游靶点损伤，从而可能导致 FSE 的长期后果。 FSE 对丘脑结构的影响可能会破坏正常的丘脑皮质网络功能，并导致行为异常和 SE 后癫痫发生。我们的结果表明，体内局灶性新皮质 SE 的单次发作会产生慢性后果，包括 VB 核中的细胞损失以及丘脑内和皮质丘脑网络中的兴奋性连接增加。其他实验将评估这些改变的功能后果以及减轻细胞损失和突触连接改变的方法。
Status epilepticus (SE) is a life-threatening emergency that can result in de novo development or worsening of epilepsy. We tested the hypothesis that the aberrant cortical output during neocortical focal status epilepticus (FSE) would induce structural and functional changes in the thalamus that might contribute to hyperexcitability in the thalamocortical circuit. We induced neocortical FSE by unilateral epidural application of convulsant drugs to the somatosensory cortex of anesthetized mice of both sexes. The resulting focal EEG ictal episodes were associated with behavioral seizures consisting of contralateral focal myoclonic activity and persisted for 2–3 h. Ten and 30 days later, brains were processed for either immunohistochemistry (IHC) or in vitro slice recordings. Sections from the center of the thalamic reticular nucleus (nRT, see methods), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM) from the ventrobasal nucleus (VB) were used to measure density of NeuN-immunoreactive neurons, GFAP-reactive astrocytes, and colocalized areas for VGLUT1 + PSD95- and VGLUT2 + PSD95-IR, presumptive excitatory synapses of cortical and thalamic origins. Whole-cell voltage-clamp recordings were used to measure spontaneous EPSC frequency in these nuclei. We found that the nRT showed no decrease in numbers of neurons or evidence of reactive astrogliosis. In contrast, there were increases in GFAP-IR and decreased neuronal counts of NeuN positive cells in VB. Dual IHC for VGLUT1-PSD95 and VGLUT2-PSD95 in VB showed increased numbers of excitatory synapses, likely of both thalamic and cortical origins. The frequency, but not the amplitude of sEPSCs was increased in nRT and VB neurons. Previous reports have shown that prolonged neocortical seizures can induce injury to downstream targets that might contribute to long-term consequences of FSE. Effects of FSE in thalamic structures may disrupt normal thalamo-cortical network functions and contribute to behavioral abnormalities and post-SE epileptogenesis. Our results show that a single episode of focal neocortical SE in vivo has chronic consequences including cell loss in VB nuclei and increased excitatory connectivity in intra-thalamic and cortico-thalamic networks. Additional experiments will assess the functional consequences of these alterations and approaches to mitigate cell loss and alterations in synaptic connectivity.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
6.1
作者：
Gu, Feng;Parada, Isabel;Prince, David A.
通讯作者：
Prince, David A.
影响因子：
2.9
作者：
Huang, Hao;Li, Ruohan;Chen, Yangmei
通讯作者：
Chen, Yangmei
影响因子：
1.9
作者：
de Jong, B. M.;van de Hoeven, J. H.;van der Naalt, J.
通讯作者：
van der Naalt, J.
影响因子：
5.6
作者：
Katramados AM;Burdette D;Patel SC;Schultz LR;Gaddam S;Mitsias PD
通讯作者：
Mitsias PD