ACETYLCHOLINE PRECURSORS ATTENUATE NEUROINFLAMMATION IN LPS-STIMULATED BV2 CELLS

Choline-containing phospholipids, choline alphoscerate (α-GPC),and cytidine 5’-diphosphocholine (CDP-choline) are both acetyl-choline precursors crossing the blood-brain barrier. As pro-cholinergic nootropic agents, studies have provided their neuro-protective effects. Currently, there is a limited number of studiesconcerning whether they have a similar effect in treating cogni-tive impairment. Indeed, contradictory results have been report-ed in their mechanisms of action on the neurovascular units.Since microglia play a crucial role in neuronal damage and pro-tection, this study investigated the effects of α-GPC and CDP-choline on the inflammatory response in activated microgliausing an immortalized murine microglial cell line (BV-2) stimu-lated with lipopolysaccharide (LPS). BV2 microglia were treat-ed with or without LPS and were incubated with LPS and dif-ferent concentrations of both acetylcholine precursors for 24 h.MTT assay, immunocytochemistry, and Western blotting methodswere utilized. MTT assay did not show significant changes in cellviability after treatments at different concentrations. Here, wereport no differences in untreated cells. On the contrary, morpho-logical changes and an increase in ionized calcium-bindingadapter molecule 1 (Iba1) expression were found in LPS-stimu-lated BV-2 cells. In addition, the nuclear translocation of nuclearfactor-kappa B (NF-κB) and the up-regulation of inflammatoryinterleukin-1β(IL-1β) were accompanied by an increase inoxidative state proteins and lipid peroxidation in LPS-treatedBV2 cells. These alterations were reversed after the treatmentswith both α-GPC and CDP-choline. Our data demonstrate thatthese compounds attenuate equally LPS-induced neuroinflam-matory responses and suggest insights to explain their therapeu-tic role in brain disorders characterized by vascular impairment.