Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice.
Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice.
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APP/PS1 和衰老小鼠的神经炎症、小胶质细胞激活和蓝斑-去甲肾上腺素系统变性的比较。
DOI：
10.1186/s12974-020-02054-2
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发表时间：
2021-01-06
影响因子：
9.3
通讯作者：
Dong H
中科院分区：
文献类型：
--
作者：
Cao S;Fisher DW;Rodriguez G;Yu T;Dong H
小胶质细胞在阿尔茨海默病（AD）发病机制中的作用变得越来越重要，因为这些细胞类型的激活可能有助于与疾病的所有阶段相关的病理和保护过程。在早期AD发病过程中，变性的第一个区域之一是蓝斑（LC），其提供中枢神经系统的广泛神经支配并促进去甲肾上腺素（NE）传递。虽然LC-NE可能影响小胶质细胞动力学，但与其他健康衰老相比，这些系统如何随着AD而变化尚不清楚。在这项研究中，我们评估了神经炎症和神经退行性变的LC-NE系统在APP/PS1小鼠和老年WT小鼠的脑和脊髓的动态变化，免疫荧光和ELISA。我们的研究结果表明，与WT小鼠相比，在APP/PS1的皮质、海马和脊髓中观察到炎性细胞因子的表达增加和小胶质细胞活化。LC-NE神经元和纤维丢失以及去甲肾上腺素转运蛋白（NET）表达减少在APP/PS1小鼠中更为明显，尽管12月龄APP/PS1和WT小鼠之间的NE水平相似。值得注意的是，与12个月和24个月大的WT小鼠相比，12个月大的APP/PS1小鼠脑和脊髓中小胶质细胞活化、LC-NE神经纤维丢失和NET减少的程度更严重。这些结果表明，APP/PS1小鼠脑和脊髓中神经炎症和小胶质细胞活化的升高与LC-NE系统的显著变性相关。
The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.
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影响因子：
--
作者：
Cao, Song;Li, Juan;Yu, Tian
通讯作者：
Yu, Tian
DOI：
10.1073/pnas.1616515114
发表时间：
2016-12-20
影响因子：
11.1
作者：
Kempadoo, Kimberly A.;Mosharov, Eugene V.;Kandel, Eric R.
通讯作者：
Kandel, Eric R.
DOI：
10.1007/s11481-019-09885-8
发表时间：
2020-06
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Aksenova M;Sybrandt J;Cui B;Sikirzhytski V;Ji H;Odhiambo D;Lucius MD;Turner JR;Broude E;Peña E;Lizarraga S;Zhu J;Safro I;Wyatt MD;Shtutman M
通讯作者：
Shtutman M
影响因子：
5.6
作者：
Bravo, Lidia;Torres-Sanchez, Sonia;Berrocoso, Esther
通讯作者：
Berrocoso, Esther
影响因子：
4.3
作者：
Gannon M;Che P;Chen Y;Jiao K;Roberson ED;Wang Q
通讯作者：
Wang Q