Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
1534718
Reference Type
Journal Article
Title
Palmitoylethanolamide Protects Against the Amyloid-beta 25-35-Induced Learning and Memory Impairment in Mice, an Experimental Model of Alzheimer Disease
Author(s)
D'Agostino, G; Russo, R; Avagliano, C; Cristiano, C; Meli, R; Calignano, A
Year
2012
Is Peer Reviewed?
1
Journal
Neuropsychopharmacology
ISSN:
0893-133X
EISSN:
1740-634X
Volume
37
Issue
7
Page Numbers
1784-1792
Language
English
PMID
22414817
DOI
10.1038/npp.2012.25
Web of Science Id
WOS:000304045700022
Abstract
Alzheimer disease (AD) is the most common form of neurodegenerative dementia. Amyloid-β deposition, neurofibrillary tangle formation, and neuro-inflammation are the major pathogenic mechanisms that in concert lead to memory dysfunction and decline of cognition. Palmitoylethanolamide (PEA) is the naturally occurring lipid amide between palmitic acid and ethanolamine. Despite its clear role in inflammation and pain control, only limited in vitro evidence exist about a role for PEA in neurodegenerative diseases. Here we describe the neuroprotective activities of PEA in mice injected intracerebroventricularly with amyloid-β 25-35 (Ab25-35) peptide (9 nmol). We used spatial and non-spatial memory tasks to evaluate learning and memory dysfunctions. Ab25-35 injection significantly impaired spontaneous alternation performances, water maze spatial reference and working-like memory, and novel object recognition test. PEA was administered once a day (3-30 mg/kg, subcutaneously), starting 3 h after Ab25-35, for 1 or 2 weeks. PEA reduced (10 mg/kg) or prevented (30 mg/kg) behavioral impairments induced by Ab25-35 injection. PEA failed to rescue memory deficits induced by Ab25-35 injection in peroxisome proliferator-activated receptor-α (PPAR-α) null mice. GW7647 (2-(4-(2-(1-cyclohexanebutyl)-3-cyclohexylureido)ethyl)phenylthio)-2-methylpropionic acid; 5 mg/kg per day), a synthetic PPAR-α agonist, mimicked the effect of PEA. Acute treatment with PEA was ineffective. According with the neuroprotective profile of PEA observed during behavioral studies, experimental molecular and biochemical markers induced by Ab25-35 injection, such as lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, and caspase3 activation, were reduced by PEA treatment. These data disclose novel findings about the therapeutic potential of PEA, unrevealing a previously unknown therapeutic possibility to treat memory deficits associated with AD.
Keywords
fatty acid acyl ethanolamine; peroxisome proliferator-activated receptors; hippocampus; water maze; Y-maze; dementia
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity