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兴奋性过高的潜在机制:在齿状回神经网络模型中结合苔藓纤维发芽和苔藓细胞丢失

Mechanisms Underlying Hyperexcitability: Combining Mossy Fiber Sprouting and Mossy Cell Loss in Neural Network Model of the Dentate Gyrus.

作者信息

Świetlik Dariusz

机构信息

Division of Biostatistics and Neural Networks, Medical University of Gdansk, Debinki 1 St., 80-211 Gdansk, Poland.

出版信息

Biomedicines. 2025 Jun 9;13(6):1416. doi: 10.3390/biomedicines13061416.

DOI:10.3390/biomedicines13061416
PMID:40564135
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12190842/
Abstract

: A concussive head injury increases the likelihood of temporal lobe epilepsy through mechanisms that are not entirely understood. This study aimed to investigate how two key histopathological features shared by both TLE (temporal lobe epilepsy) and head injury-mossy fiber sprouting and hilar excitatory cell loss-contribute to the modulation of dentate gyrus excitability. : A computational approach was used to explore the impact of specific levels of mossy fiber sprouting and mossy cell loss, while avoiding the confounding effects of concurrent changes. The dentate gyrus model consists of 500 granule cells, 15 mossy cells, 6 basket cells and 6 hilar perforant path-associated cells. : My simulations demonstrate a correlation between the degree of mossy fiber sprouting and the number of spikes in dentate gyrus granule cells (correlations coefficient R = 0.95, < 0.0001) and other cells (correlations coefficient R = 0.99, < 0.0001). The mean values (standard deviation, SD) and 95% CI for granule cell activity in the control group and percentage 10-50% of mossy fiber sprouting groups are 376.4 (16.7) (95% CI, 374.9-377.8) vs. 463.5 (24.3) (95% CI, 461.4-465.6) vs. 514.8 (32.5) (95% CI, 511.9-517.6) vs. 555.0 (40.4) (95% CI, 551.5-558.6) vs. 633.4 (51.8) (95% CI, 628.8-637.9) vs. 701.7 (66.2) (95% CI, 695.9-707.5). The increase in mossy fiber sprouting was significantly statistically associated with an increase in granule cell activity ( < 0.01). The removal of mossy cells led to a reduction in excitability within the model network (for granule cells, correlations coefficient R = -0.40, < 0.0001). : These results are generally consistent with experimental observations, which indicate a high degree of mossy fiber sprouting in animals with a higher frequency of seizures. Whereas unlike the strong hyperexcitability effects induced by mossy fiber sprouting, the removal of mossy cells led to reduced granule cell responses to perforant path activation.

摘要

震荡性头部损伤会通过一些尚未完全明确的机制增加颞叶癫痫的发病可能性。本研究旨在探究颞叶癫痫(TLE)和头部损伤共有的两个关键组织病理学特征——苔藓纤维增生和门区兴奋性细胞丢失——如何调节齿状回的兴奋性。采用一种计算方法来探究特定程度的苔藓纤维增生和苔藓细胞丢失所产生的影响,同时避免并发变化带来的混淆效应。齿状回模型由500个颗粒细胞、15个苔藓细胞、6个篮状细胞和6个与门区穿通路径相关的细胞组成。我的模拟结果表明,苔藓纤维增生程度与齿状回颗粒细胞的放电次数之间存在相关性(相关系数R = 0.95,P < 0.0001),与其他细胞也存在相关性(相关系数R = 0.99,P < 0.0001)。对照组以及苔藓纤维增生比例为10% - 50%的各实验组中,颗粒细胞活动的平均值(标准差,SD)及95%置信区间分别为:376.4(16.7)(95% CI,374.9 - 377.8);463.5(24.3)(95% CI,461.4 - 465.6);514.8(32.5)(95% CI,511.9 - 517.6);555.0(40.4)(95% CI,551.5 - 558.6);633.4(51.8)(95% CI,628.8 - 637.9);701.7(66.2)(95% CI,695.9 - 707.5)。苔藓纤维增生的增加与颗粒细胞活动的增加在统计学上具有显著相关性(P < 0.01)。苔藓细胞的去除导致模型网络内的兴奋性降低(对于颗粒细胞,相关系数R = -0.40,P < 0.0001)。这些结果总体上与实验观察结果一致,实验观察表明癫痫发作频率较高的动物中存在高度的苔藓纤维增生。然而,与苔藓纤维增生所诱导的强烈的过度兴奋效应不同,苔藓细胞的去除导致颗粒细胞对穿通路径激活的反应减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/b6c9f32df9f4/biomedicines-13-01416-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/f04e9a5d37d0/biomedicines-13-01416-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/d20e55016d2d/biomedicines-13-01416-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/8dc5a9655b9a/biomedicines-13-01416-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/32da92d01fdc/biomedicines-13-01416-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/8648579f9d38/biomedicines-13-01416-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/1aaafe9a3892/biomedicines-13-01416-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/b6c9f32df9f4/biomedicines-13-01416-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/f04e9a5d37d0/biomedicines-13-01416-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/d20e55016d2d/biomedicines-13-01416-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/20f7fddd5af2/biomedicines-13-01416-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/8dc5a9655b9a/biomedicines-13-01416-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/32da92d01fdc/biomedicines-13-01416-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/8648579f9d38/biomedicines-13-01416-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/1aaafe9a3892/biomedicines-13-01416-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da1/12190842/b6c9f32df9f4/biomedicines-13-01416-g008.jpg

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本文引用的文献

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Field EPSPs of Dentate Gyrus Granule Cells Studied by Selective Optogenetic Activation of Hilar Mossy Cells in Hippocampal Slices.通过海马切片中齿状回苔藓细胞的选择性光遗传学激活研究齿状回颗粒细胞的场兴奋性突触后电位
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Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.齿状回神经元 MeCP2 调节颞叶癫痫小鼠的苔藓纤维发芽。
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Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE.
齿状回沉默通过 NDR2 激酶抑制戊四氮点燃颞叶癫痫大鼠模型的苔藓纤维发芽并防止癫痫发生。
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A Hippocampal-Entorhinal Cortex Neuronal Network for Dynamical Mechanisms of Epileptic Seizure.用于癫痫发作动态机制的海马-内嗅皮层神经元网络。
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Adult-Born Granule Cells Contribute to Dentate Gyrus Circuit Reorganization after Traumatic Brain Injury.成年新生颗粒细胞有助于创伤性脑损伤后齿状回回路重组。
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Brain-wide reconstruction of inhibitory circuits after traumatic brain injury.创伤性脑损伤后抑制性回路的全脑重建。
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Virtual Therapy with the NMDA Antagonist Memantine in Hippocampal Models of Moderate to Severe Alzheimer's Disease, in Silico Trials.在中重度阿尔茨海默病海马模型中使用N-甲基-D-天冬氨酸(NMDA)拮抗剂美金刚进行虚拟治疗的计算机模拟试验
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