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-alpha (TNF-alpha)] 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.

Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer's Disease

Beggiato, Sarah
Primo
;
Tomasini, Maria Cristina
Secondo
;
Ferraro, Luca
Ultimo
2020

Abstract

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-alpha (TNF-alpha)] 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.
2020
Beggiato, Sarah; Tomasini, Maria Cristina; Cassano, Tommaso; Ferraro, Luca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2419930
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