Choline alphoscerate and thioctic acid eff ects on neuroinfl ammation in lipopolysaccharide-stimulated BV2 microglial cells

Choline alphoscerate (α-GPC) is a choline-containing phospholipid and an acetylcholine precursor enhancing cognition [1]. Th ioctic acid (TIO) is a potent antioxidant with the ability to promote neuronal proliferation, and the eutomer (+)-TIO is more active than the racemic form or (−)-enantiomer to counter neuronal damage [2]. Th us, both these compounds have previously been shown to exhibit neuroprotection [2,3]. Since microglia plays a crucial role in brain development, homeostasis, and disease, this study investigated the eff ects of α-GPC and the (+)-TIO on the infl ammatory response in BV2 culture cells, a cell line of murine microglia origin, stimulated with lipopolysaccharide (LPS). BV2 microglia were treated with or without LPS and were incubated with LPS and α-GPC and (+)-TIO alone or in the association for 24 h. MTT assay, immunocytochemistry, and western blotting methods were utilized. MTT assay did not show signifi cant changes in cell viability aft er treatments at diff erent concentrations in unstimulated cells. On the contrary, LPS triggered morphological changes and an increase in ionized calcium-binding adapter molecule-1 (Iba-1) expression in BV2 cells. Moreover, an up-regulation of the nuclear factor-kappa B (NF-κB) and the interleukin-1β (IL-1β) were found in LPS-treated BV2 cells. Th ese alterations were reversed by the treatment with α-GPC alone but not with (+)-TIO. Th e mechanism underlying α-GPCmediated attenuation of inflammation in BV2 cells appeared to involve the suppression of translocation of NF-κB into the nucleus. In conclusion, we provide evidence that α-GPC attenuates LPS-induced neuroinfl ammatory responses, and this suggests that it may have therapeutic potential for the treatment of neurodegenerative diseases that are accompanied by microglial activation. References [1] Traini E, Bramanti V, Amenta F. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profi le as cognition enhancing agent. Curr Alzheimer Res. 2013;10(10):1070-9. [2] Pacini A, Tomassoni D, Trallori E, Micheli L, Amenta F, Ghelardini C, Di Cesare Mannelli L, Traini E. Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Th ioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial. Front Pharmacol. 2021;12:607572. [3] Roy P, Tomassoni D, Nittari G, Traini E, Amenta F. Eff ects of choline containing phospholipids on the neurovascular unit: A review. Front Cell Neurosci. 2022;16:988759.