Contribution of 25-hydroxycholesterol to the cross-interaction of the immune and nervous systems

Abstract

25-hydroxycholesterol (25HC) is produced from cholesterol by cholesterol-25-hydroxylase, the expression of which, like the level of 25HC, increases significantly in macrophages, dendritic cells and microglia during an inflammatory reaction. In turn, 25HC acts on many immune cells, therefore it can modulate the course of the inflammatory reaction and prevent the penetration of viruses into cells. Data are accumulating about of the participation of 25HC in the regulation of synaptic transmission in both the central and peripheral nervous systems. Production of 25HC is increased not only during inflammation, but in a number of neurodegenerative diseases (Alzheimer's disease and amyotrophic lateral sclerosis), so this HC can be important, on the one hand, in the adaptation of synaptic activity to inflammatory conditions, and on the other in the pathogenesis of neurodegenerative diseases and the formation of synaptic dysfunctions. The main targets of 25HC in the nervous system are glutamate NMDA-receptors, liver X receptors and estrogen receptors. In addition, 25HC can directly influence on the properties of synaptic membranes by changing the formation of membrane microdomains (lipid rafts) where proteins are clustered that important for synaptic plasticity. Current data indicate that the effects of 25HC strongly depend on its concentration and the context (norm, pathology, presence of an inflammatory reaction) in which the effect of 25HC is being investigated. In this mini-review we focused on the key aspects of the action of 25HC as a local regulator of cholesterol homeostasis and a paracrine molecule that realize the effect of inflammation on neurotransmission processes in the central and peripheral nervous systems.