Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi, 563000, Guizhou, China.
Guizhou Key Lab of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical University, 6 West Xuefu Street, Zunyi, 563002, Guizhou, China.
J Neuroinflammation. 2021 Jan 6;18(1):10. doi: 10.1186/s12974-020-02054-2.
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.
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与疾病所有阶段相关的病理和保护过程都有关系。在 AD 发病的早期，首先发生变性的区域之一是蓝斑（LC），它为中枢神经系统提供广泛的神经支配，并促进去甲肾上腺素（NE）的传递。尽管 LC-NE 可能会影响小胶质细胞的动力学，但尚不清楚与健康衰老相比，这些系统在 AD 中如何变化。
在这项研究中，我们使用免疫荧光和 ELISA 评估了 APP/PS1 小鼠和老年 WT 小鼠大脑和脊髓中 LC-NE 系统的神经炎症和神经退行性变的动态变化。
我们的结果表明，与 WT 小鼠相比，APP/PS1 小鼠的大脑皮层、海马体和脊髓中观察到炎症细胞因子表达增加和小胶质细胞激活。尽管 12 个月龄 APP/PS1 小鼠和 WT 小鼠之间的 NE 水平相似，但 LC-NE 神经元和纤维丢失以及去甲肾上腺素转运体（NET）表达减少更为明显。值得注意的是，12 个月龄 APP/PS1 小鼠大脑和脊髓中的小胶质细胞激活程度、LC-NE 神经纤维丢失和 NET 减少比 12 个月龄和 24 个月龄 WT 小鼠更为严重。
这些结果表明，APP/PS1 小鼠大脑和脊髓中的神经炎症和小胶质细胞激活程度与 LC-NE 系统的显著退化相关。
