Relationship between chronic treatment with lithium and the role of cholinergic system in neuroinflammation

Abstract

Since the world population is getting older, there is a proportional increase in the prevalence of dementia, particularly Alzheimer's disease (AD), progressive and irreversible neurodegenerative disorder that results in significant memory loss.One of the currently most accepted hypothesis for the etiology of AD is the cholinergic one, which suggests that cognitive decline is due to loss of cholinergic neurons. Lithium is a monovalent cation whose efficacy in stabilizing mood was discovered over 50s. Studies have shown that chronic treatment with this ion increased uptake of choline by presynaptic terminals and cholinergic transmission, and reduced the toxicity caused by complexes formed by beta-amyloid and the enzyme cholinesterase. Moreover, in recent clinical study of our group, we found that treatment with lithium microdoses was efficient in preventing the progression of cognitive decline in patients with clinical diagnosis for Alzheimer's disease.This project aims to clarify the mechanisms involved in the recent clinical effects observed with treatment with lithium microdoses, analyzing a possible synergism between the inhibition of GSK-3 and increased activation of a7 receptors in microglia, leading to reduced neuroinflammatory process, which will be induced by an injection of lipopolysaccharide. This study may provide basis for understanding the mechanisms by which lithium participates in the stabilization of dementia, which can contribute to new treatment options for AD.