Effect of palmitoylethanolamide on astrocyte activity in a triple transgenic model of Alzheimer’s disease

Alzheimer's disease (AD) is a neurodegenerative disorder that slowly leads patients to functional disability. It is characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles which cause neuronal loss and synapses reduction. Recently, research focused on neurodegeneration changed its target, considering the role of non-neuronal cells in promoting disease progression; in fact, a continuous astrocyte activation named "reactive gliosis" is a typical AD feature. Many in vivo models have been developed to reproduce at best the hallmarks of AD and one of these is the 3xTg-AD. Aim of the study was to investigate any differences of the principal astrocyte activation markers in 3xTg-AD mice, compared to Non-Tg ones, later on evaluating the action of palmitoylethanolamide (PEA), an endogenous lipidic compound with already established anti-inflammatory properties. We found an increased activation of 3xTg-AD astrocytes when compared to Non-Tg, imputable to an increased glial fibrillary acidic protein (GFAP) expression. PEA was capable to control reactive gliosis, leading cell's functionality to a physiological state. These results strongly candidate PEA as a promising tool in the therapeutic strategy against AD.