Expression Profiling of Cytokine, Cholinergic Markers, and Amyloid-β Deposition in the APPSWE/PS1dE9 Mouse Model of Alzheimer’s Disease Pathology

Abstract

Background:Alzheimer’s disease (AD), a neurodegenerative disease, is associated with dysfunction of the olfactory and the entorhinal cortex of the brain that control memory and cognitive functions and other daily activities. Pro-inflammatory cytokines, amyloid-β (Aβ), and the cholinergic system play vital roles in the pathophysiology of AD. However, the role of changes in cholinergic system components, Aβ accumulation, and cytokines in both the olfactory and entorhinal cortex is not known clearly.Objective:The present study is aimed to evaluate the changes of cholinergic system components, Aβ accumulation, and cytokines in both the olfactory bulb (OB) and entorhinal cortex (EC) of young and aged APPSWE/PS1dE9 transgenic (Tg) mice.Methods:We have explored the changes of cholinergic system components, Aβ accumulation, and expression profiling of cytokines in the OB and EC of aged APPswe transgenic mice and age-matched wild type mice using quantitative Real-Time PCR assays and immunohistochemistry techniques.Results:In aged Tg mice, a significant increase of expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and chemokine MCP1 (p < 0.001, p < 0.001, and p = 0.001, respectively) and a significant reduction of nAChRα4 (p = 0.048) and AChE (p = 0.023) was observed when compared with age-matched wild type mice. Higher levels of AChE and BuChE are expressed in OB and EC of the APPSWE/PS1dE9 of Tg mice. Aβ accumulation was observed in OB and EC of the APPSWE/PS1dE9 of Tg mice.Conclusion:The study demonstrates the expression profiling of pro-inflammatory cytokines and cholinergic markers as well as Aβ accumulation in OB and EC of the APPSWE/PS1dE9 Tg mice. Moreover, the study also demonstrated that the APPSWE/PS1dE9 Tg mice can be useful as a mouse model to understand the role of pro-inflammatory cytokines and cholinergic markers in pathophysiology of AD.

Effect of Clostridium butyricum against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate

“…Activation of microglia also played an important role in the progression of brain disorders, and the activated microglia produced excess proinflammatory cytokines, such as IL‐1β and TNF‐α, which ultimately induced neurodegeneration . The levels of proinflammatory cytokines in the AD patients and model mice were significantly increased, and excess inflammatory cytokines further exacerbated the pathological processes of AD . In this study, CB suppressed microglia activation and decreased levels of IL‐1β and TNF‐α in the APP/PS1 mice.…”

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

“…An increasing number of studies indicating a role of inflammation and immunity in the pathogenesis of symptoms of schizophrenia have provided evidence that systemic inflammation can exert a profound influence on the brain that leads to changes in mood, cognition, and behavior. In this regard, the peripheral immune system-to-brain communication pathways have been studied extensively in the context of other neuroinflammmatory diseases in which inflammatory cytokines are, likewise, considered to play a critical role (15)(16)(17). Several hypotheses have been formulated to both highlight and account for the involvement of immune cells and cytokines in schizophrenia.…”

The Effects of Crinum asiaticum var. japonicum Baker Seeds on Neuroprotection and Antineuroinflammation in Neuronal Cell Lines

“…Aβ and AChE are central biomarkers for AD. 25 In the brain of AD patients, extracellular plaques of aggregated Aβ proteins are observed and contribute to neurodegeneration. Acute exposure to Aβ has no toxic effect, whereas long-term exposure mediates cholinergic cellular toxicity.…”