Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3×Tg-AD mice.
Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3×Tg-AD mice.
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慢性颞叶癫痫与3×TG-AD小鼠的阿尔茨海默氏症神经病理学增强有关。
DOI：
10.1371/journal.pone.0048782
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Patrylo PR
中科院分区：
文献类型：
--
作者：
Yan XX;Cai Y;Shelton J;Deng SH;Luo XG;Oddo S;Laferla FM;Cai H;Rose GM;Patrylo PR
The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of growing interest. Senile plaques and tauopathy are found in epileptic human temporal lobe structures, and individuals with AD have an increased incidence of spontaneous seizures. However, why and how epilepsy is associated with enhanced AD-like pathology remains unknown. We have recently shown β-secretase-1 (BACE1) elevation associated with aberrant limbic axonal sprouting in epileptic CD1 mice. Here we sought to explore whether BACE1 upregulation affected the development of Alzheimer-type neuropathology in mice expressing mutant human APP, presenilin and tau proteins, the triple transgenic model of AD (3×Tg-AD). 3×Tg-AD mice were treated with pilocarpine or saline (i.p.) at 6–8 months of age. Immunoreactivity (IR) for BACE1, β-amyloid (Aβ) and phosphorylated tau (p-tau) was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed of BACE1-labeled swollen/sprouting axons and extracellular AβIR were seen in the hippocampal formation, amygdala and piriform cortices of 9 month-old epileptic, but not control, 3×Tg-AD mice. Densities of plaque-associated BACE1 and AβIR were elevated in epileptic versus control mice at 11 and 14 months of age. p-Tau IR was increased in dentate granule cells and mossy fibers in epileptic mice relative to controls at all time points examined. Thus, pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced neuritic plaque formation and altered intraneuronal p-tau expression in temporal lobe structures in 3×Tg-AD mice, with these pathologies occurring in regions showing neuronal death and axonal dystrophy.
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DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
9.9
作者：
Buda, O.;Arsene, D.;Curca, G. C.
通讯作者：
Curca, G. C.
第一嗅觉传递周围与年龄相关的轴突末端病理，涉及淀粉样蛋白过度表达但无斑块形成
影响因子：
3.3
作者：
Cai, Y.;Xue, Z. -Q.;Yan, X. -X.
通讯作者：
Yan, X. -X.
影响因子：
2.5
作者：
Cavazos, JE;Zhang, PS;Sutula, TP
通讯作者：
Sutula, TP
影响因子：
25
作者：
Bero AW;Yan P;Roh JH;Cirrito JR;Stewart FR;Raichle ME;Lee JM;Holtzman DM
通讯作者：
Holtzman DM