{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:23:10Z","timestamp":1790886190090,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T00:00:00Z","timestamp":1331251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T00:00:00Z","timestamp":1331251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>In addition to cytotoxic mechanisms directly impacting neurons, \u03b2-amyloid (A\u03b2)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-\u03b1 (PPAR\u03b1).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Findings<\/jats:title>\n            <jats:p>In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of A\u03b2 neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with A\u03b2<jats:sub>1-42<\/jats:sub> and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPAR\u03b1 and PPAR\u03b3 antagonists, respectively. The results indicate that PEA is able to blunt A\u03b2-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPAR\u03b1 activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPAR\u03b1 mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during A\u03b2 challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce A\u03b2-evoked neuroinflammation and attenuate its neurodegenerative consequences.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-2094-9-49","type":"journal-article","created":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T11:14:32Z","timestamp":1331291672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated 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