Electrophysiological changes precede morphological changes to frontal cortical pyramidal neurons in the rTg4510 mouse model of progressive tauopathy.
Electrophysiological changes precede morphological changes to frontal cortical pyramidal neurons in the rTg4510 mouse model of progressive tauopathy.
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电生理变化先于形态学变化，其在RTG4510进行性tauopathy的RTG4510小鼠模型中的额叶皮质神经元。
DOI：
10.1007/s00401-012-1038-9
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发表时间：
2012-12
影响因子：
12.7
通讯作者：
Luebke JI
中科院分区：
文献类型：
--
作者：
Crimins JL;Rocher AB;Luebke JI
使用全细胞膜片钳记录和高分辨率形态测量来评估从rTg 4510 tau突变（P301 L）小鼠制备的额叶皮质切片中的tau蛋白病的早期（< 4个月）和晚期（> 8个月）阶段的第3层锥体神经元的功能和结构特性。在早期tau蛋白病中，树突状结构被保留。在晚期tau蛋白病中，神经元可被分类为“萎缩性”（58%）-表现出顶端簇的显著萎缩，或“完整的”（42%）-具有正常的顶端簇，并且在某些情况下，顶端干的斜分支的增殖性发芽。大约相等数量的萎缩和完整的神经元含有神经元缠结（NFT）或无缠结，进一步支持NFT本身无毒的观点。由于蘑菇棘的特定减少，棘密度降低，但萎缩和完整神经元的丝状伪足增加。通过对比这些形态学的变化，这是强大的，只有在先进的阶段，显着的电生理变化存在于早期阶段，并坚持在先进的阶段，在萎缩和完整的神经元。这些变化中最显著的是：去极化静息膜电位、增加的去极化下垂电位和增加的动作电位放电率-所有这些都表明过度兴奋。自发兴奋性突触后电流的频率或幅度在任何阶段都不会降低。功能上重要的电生理变化与退行性形态学变化的时间过程的差异意味着进行性tau蛋白病期间神经元功能和结构变化的致病机制的差异。
Whole-cell patch-clamp recordings and high resolution morphometry were used to assess functional and structural properties of layer 3 pyramidal neurons in early (< 4 months) and advanced (> 8 months) stages of tauopathy in frontal cortical slices prepared from rTg4510 tau mutant (P301L) mice. In early tauopathy, dendritic architecture is preserved. In advanced tauopathy, neurons can be categorized as either “atrophic” (58%)- exhibiting marked atrophy of the apical tuft, or “intact” (42%)- with normal apical tufts and, in some instances, proliferative sprouting of oblique branches of the apical trunk. Approximately equal numbers of atrophic and intact neurons contain neurofibrillary tangles (NFTs) or are tangle-free, lending further support to the idea that NFTs per se are not toxic. Spine density is decreased due to a specific reduction in mushroom spines, but filopodia are increased in both atrophic and intact neurons. By contrast to these morphological changes, which are robust only in the advanced stage, significant electrophysiological changes are present in the early stage and persist in the advanced stage in both atrophic and intact neurons. The most marked of these changes are: a depolarized resting membrane potential, an increased depolarizing sag potential and increased action potential firing rates- all indicative of hyperexcitability. Spontaneous excitatory postsynaptic currents are not reduced in frequency or amplitude in either stage. The difference in the time course of functionally important electrophysiological changes versus regressive morphological changes implies differences in pathogenic mechanisms underlying functional and structural changes to neurons during progressive tauopathy.
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表达人类野生型Tau的转基因小鼠的树突复杂性和脊柱形态的变化。
影响因子：
3.1
作者：
Dickstein, Dara L.;Brautigam, Hannah;Stockton, Steven D., Jr.;Schmeidler, James;Hof, Patrick R.
通讯作者：
Hof, Patrick R.
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：
6
作者：
Kopeikina, Katherine J.;Carlson, George A.;Spires-Jones, Tara L.
通讯作者：
Spires-Jones, Tara L.
DOI：
10.1073/pnas.94.1.298
发表时间：
1997-01-07
影响因子：
11.1
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
4.2
作者：
FLOOD, DG;COLEMAN, PD
通讯作者：
COLEMAN, PD