Effects of altered tau expression on dentate granule cell excitability in mice.
Effects of altered tau expression on dentate granule cell excitability in mice.
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DOI：
10.1016/j.expneurol.2021.113766
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发表时间：
2021-09
影响因子：
5.3
通讯作者：
Smith BN
中科院分区：
文献类型：
--
作者：
Cloyd RA;Koren J 3rd;Abisambra JF;Smith BN
tau病变，包括阿尔茨海默病，其特征是与认知和行为障碍发病相关的过度磷酸化和病理性tau蛋白的进行性积累。Tau病理也与癫痫发作和癫痫易感性增加有关，Tau - / -小鼠在一些癫痫模型中表现出癫痫抵抗。为了更好地了解tau病理与神经元兴奋性的关系，我们对表达tau - / -和人类tau的htau小鼠的齿状回颗粒细胞进行了全细胞膜片钳电生理学研究。htau小鼠与其他转基因tau模型的独特之处在于，内源性小鼠tau基因已被容易磷酸化的人类tau取代。我们评估了tau - / -、htau和非转基因小鼠在1.5个月、4个月和9个月大时的齿状颗粒细胞中神经元兴奋性的几种测量方法，包括诱发动作电位频率和兴奋性突触反应。与年龄匹配的对照组相比，来自tau−/−和htau小鼠的齿状颗粒细胞的诱发动作电位峰值频率较低，配对脉冲易化程度较高，表明神经元兴奋性降低。我们的研究结果表明，与病理性tau蛋白的存在相比，功能性tau蛋白的缺失对神经元兴奋性的影响更大。这些结果还表明，tau对神经元兴奋性的影响比以前所理解的要复杂得多。
Tauopathies, including Alzheimer’s disease, are characterized by progressive accumulation of hyperphosphorylated and pathologic tau protein in association with onset of cognitive and behavioral impairment. Tau pathology is also associated with increased susceptibility to seizures and epilepsy, with tau−/− mice showing seizure resistance in some epilepsy models. To better understand how tau pathology is related to neuronal excitability, we performed whole-cell patch clamp electrophysiology in dentate gyrus granule cells of tau−/− and human-tau expressing, htau mice. The htau mouse is unique from other transgenic tau models in that the endogenous murine tau gene has been and replaced with readily phosphorylated human tau. We assessed several measures of neuronal excitability, including evoked action potential frequency and excitatory synaptic responses in dentate granule cells from tau−/−, htau, and non-transgenic control mice at 1.5, 4, and 9 months of age. Compared to age matched controls, dentate granule cells from both tau−/− and htau mice had a lower peak frequency of evoked action potentials and greater paired pulse facilitation, suggesting reduced neuronal excitability. Our results suggest that neuronal excitability is more strongly influenced by the absence of functional tau than by the presence of pathologic tau. These results also suggest that tau’s effect on neuronal excitability is more complex than previously understood.
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影响因子：
12.7
作者：
Hatch RJ;Wei Y;Xia D;Götz J
通讯作者：
Götz J
DOI：
10.1523/jneurosci.3191-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Holth JK;Bomben VC;Reed JG;Inoue T;Younkin L;Younkin SG;Pautler RG;Botas J;Noebels JL
通讯作者：
Noebels JL
影响因子：
6.1
作者：
Garcia-Cabrero, Ana M.;Guerrero-Lopez, Rosa;Sanchez, Marina P.
通讯作者：
Sanchez, Marina P.
影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
影响因子：
5.3
作者：
DeVos, Sarah L.;Goncharoff, Dustin K.;Miller, Timothy M.
通讯作者：
Miller, Timothy M.