Bibliographic
N-palmitoylethanolamide (PEA) is a lipid mediator belonging to the class of the N-acylethanolamine. Products containing PEA, also in ultramicronized formulation (um-PEA), are already licensed for use in humans for its analgesic and anti-inflammatory properties, and demonstrated high safety and tolerability. Preclinical studies indicate that PEA, especially in the ultramicronized form, could be a potential therapeutic agent for Alzheimer’s disease (AD). In this study, we evaluated the neuroprotective and antioxidant effects of chronic (three months) um-PEA administration in an animal model of AD (3xTg-AD mice). For translation purposes, the compound has been orally administered. Cognitive performance as well as biochemical markers [(interleukin-16 (IL-16) and tumor necrosis factor-α (TNF-α)] levels, reactive oxygen species (ROS) production, synaptophysin and glutamate levels) have been evaluated at the end of um-PEA treatment. The results indicate that orally administered um-PEA was adsorbed and distributed in the mice brain. The chronic treatment with um-PEA (100 mg/kg/day for three months) rescued cognitive deficit, restrained neuroinflammation and oxidative stress, and reduced the increase in hippocampal glutamate levels observed in 3xTg-AD mice. Overall, these data reinforce the concept that um-PEA exerts beneficial effects in 3xTg-AD mice. The fact that PEA is already licensed for the use in humans strongly supports its rapid translation in clinical practice.
Therapeutic Agent
An ultramicronized formulation of PEA was used in this study. This formulation is shown to have increased bioavailability (S. Petrosino and V. Di Marzo, “The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations,” British Journal of Pharmacology, vol. 174, no. 11, pp. 1349–1365, 2017).
Animal Model
Experimental Design
Inclusion/Exclusion Criteria: Mice that did not explore both objects during the training phase of the novel object recognition test were excluded from further analysis.