Abstract
BackgroundNeuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease (AD), particularly in amyloid-β (Aβ) production. But the impact of the cytokine, interleukin-17A (IL-17) on the course of AD has not been well defined. The goal was to determine the effect of IL-17 on neural damage and whether IL-17 inhibitor (Y-320) could ameliorate Aβ-induced neurotoxicity and cognitive decline.MethodsThe expression level of IL-17 was analyzed in APP/PS1 mice. Then IL-17 was injected into the lateral ventricle of C57BL WT mice and roles on synaptic dysfunction and cognitive impairments were examined. Aβ42 was injected into the lateral ventricle of to mimic Aβ42 model mice. The effects of IL-17 inhibitor by oral gavage on Aβ42-induced neurotoxicity and cognitive decline were examined. ResultsWe found that IL-17 was increased in the hippocampus of APP/PS1 transgenic mouse, which has a fundamental role in mediating brain damage in neuroinflammatory processes. Furthermore, we reported that IL-17 was administrated in primary hippocampal neurons, leading to neural damage and synaptic dysfunction. At the same time, IL-17 caused synaptic dysfunction and cognitive impairments accompanying with increased of Aβ levels in mice. In addition, we found that Y-320 could rescue Aβ42–induced neural damage in primary hippocampal neurons, and ameliorate neuronal damage and cognitive impairments in Aβ42 model mice. Interestingly, we observed that IL-17 upregulated the production of soluble amyloid precursor protein β (sAPPβ) and phosphorylation of APP at T668 (pT668), moreover, Y-320 inhibited the Aβ production by down-regulation the sAPPβ and pT668. Conclusions Blockage of IL-17 might ameliorate Aβ-induced neurotoxicity and cognitive decline. These results strongly demonstrate a potential therapeutic role for IL-17 inhibitor in AD.
Cocaine Exposure Results in Formation of Dendritic Varicosity in Rat Primary Hippocampal Neurons
