The role of glial cells in neuroinflammation in the context of Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the world’s leading form of dementia. The pathogenesis of AD includes increased brain levels of β‐amyloid peptide oligomers (AβOs), neurotoxins associated with AD. The increase in oligomer concentration is neurotoxic and causes, among the damages, synapse loss, mitochondrial dysfunction and impairment of proteostasis mechanisms. Neuroinflammation, notably the activation of microglia and astrocytes to pro‐inflammatory states, has been associated with the pathogenesis of several neurodegenerative diseases. The current work aimed to evaluate the neuroprotective role of microglia in the context of the pathophysiology of AD.MethodThis study aims to investigate potential modulations in morphology and function of glial cells in experimental models of Alzheimer’s disease (AD), evaluating (1) the in vitro activation of microglia and astrocytes promoted by AβOs, and (2) in vivo microglia and/or astrocytic activation in mice receiving intracerebroventricular (icv) administration of AβOs. Expression of cytokines and glial markers were analyzed by RT PCR and Immunocytochemistry.ResultPreliminary results suggest an increase in glial activation markers, such as GFAP and F4/80, and complement immune system markers such as C1q, 7 days after icv infusion of AβOs. No significant differences were observed in the expression of TNF‐α. Immunocytochemical analyzes suggest greater nuclear factor‐KB translocation in microglial cells treated with AβOs compared to vehicle.ConclusionResults are consistent with an important role of glial cells in the pathogenesis of AD, with glial activity altered and activated in both in vitro and in vivo models. In the face of chronic processes, these cells can remain in an activated state, releasing cytokines, complement components and chemokines, which may contribute to the production and accumulation of Aβ and further exacerbate pathology.