Emergence of early alterations in network oscillations and functional connectivity in a tau seeding mouse model of Alzheimer's disease pathology.
Emergence of early alterations in network oscillations and functional connectivity in a tau seeding mouse model of Alzheimer's disease pathology.
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DOI：
10.1038/s41598-017-13839-6
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发表时间：
2017-10-27
影响因子：
4.6
通讯作者：
Drinkenburg WH
中科院分区：
文献类型：
--
作者：
Ahnaou A;Moechars D;Raeymaekers L;Biermans R;Manyakov NV;Bottelbergs A;Wintmolders C;Van Kolen K;Van De Casteele T;Kemp JA;Drinkenburg WH
突触功能障碍和断开连接是阿尔茨海默病（AD）的核心缺陷，在组织病理学和认知功能发生明显变化之前。本研究在P301L小鼠中研究了tau病理诱导对功能网络连通性的早期和晚期影响。使用多通道脑电图振荡来计算(1)前额皮质（PFC）和海马（HPC） CA1-CA3网络之间的相干活动；(2) θ和γ振荡之间的相幅交叉频率耦合（PAC），有助于充分的认知功能；(3)被动奇球错配样负性（MMN）范式下的听觉诱发电位和振荡对信息加工的评价。最后用免疫组化法测定tau聚集和GABA小白蛋白（PV+）中间神经元的密度。从第2周开始，PFC和HPC CA1之间的脑电图θ振荡和相干活动早期减弱，θ - γ振荡PAC急剧受损，而PV+中间神经元计数没有改变。此外，tau病理破坏了MMN复合体的振幅，诱发了标准和异常刺激下的伽马振荡，表明记忆形成和回忆发生了改变。通过tau种子注射诱导细胞内tau聚集导致早期连接改变和强烈的θ - γ振荡解耦，这可能是功能失调神经元网络的早期电生理特征。
Synaptic dysfunction and disconnectivity are core deficits in Alzheimer’s disease (AD), preceding clear changes in histopathology and cognitive functioning. Here, the early and late effects of tau pathology induction on functional network connectivity were investigated in P301L mice. Multichannel EEG oscillations were used to compute (1) coherent activity between the prefrontal cortex (PFC) and hippocampus (HPC) CA1-CA3 networks; (2) phase-amplitude cross frequency coupling (PAC) between theta and gamma oscillations, which is instrumental in adequate cognitive functioning; (3) information processing as assessed by auditory evoked potentials and oscillations in the passive oddball mismatch negativity-like (MMN) paradigm. At the end, the density of tau aggregation and GABA parvalbumin (PV+) interneurons were quantified by immunohistochemistry. Early weakening of EEG theta oscillations and coherent activity were revealed between the PFC and HPC CA1 and drastic impairments in theta–gamma oscillations PAC from week 2 onwards, while PV+ interneurons count was not altered. Moreover, the tau pathology disrupted the MMN complex amplitude and evoked gamma oscillations to standard and deviant stimuli suggesting altered memory formation and recall. The induction of intracellular tau aggregation by tau seed injection results in early altered connectivity and strong theta–gamma oscillations uncoupling, which may be exploited as an early electrophysiological signature of dysfunctional neuronal networks.
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影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
5.3
作者：
Canuet, Leonides;Pusil, Sandra;Maestu, Fernando
通讯作者：
Maestu, Fernando
影响因子：
4.7
作者：
Ahnaou, A.;Huysmans, H.;Drinkenburg, W. H. I. M.
通讯作者：
Drinkenburg, W. H. I. M.
影响因子：
9.9
作者：
Dickerson, B. C.;Stoub, T. R.;deToledo-Morrell, L.
通讯作者：
deToledo-Morrell, L.