Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease
Palmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer...
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2021-09-01
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doaj-ed043e7773534734a848874c29ef353a2021-09-29T04:35:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.748021748021Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s DiseaseVanessa D’Antongiovanni0Carolina Pellegrini1Luca Antonioli2Laura Benvenuti3Clelia Di Salvo4Lorenzo Flori5Rebecca Piccarducci6Simona Daniele7Alma Martelli8Alma Martelli9Alma Martelli10Vincenzo Calderone11Vincenzo Calderone12Vincenzo Calderone13Claudia Martini14Matteo Fornai15Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyInterdepartmental Research Center “Nutrafood: Nutraceutica e Alimentazione per la Salute”, University of Pisa, Pisa, ItalyInterdepartmental Research Center “Biology and Pathology of Ageing”, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyInterdepartmental Research Center “Nutrafood: Nutraceutica e Alimentazione per la Salute”, University of Pisa, Pisa, ItalyInterdepartmental Research Center “Biology and Pathology of Ageing”, University of Pisa, Pisa, ItalyDepartment of Pharmacy, University of Pisa, Pisa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyPalmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer’s disease (AD) are lacking. This study was designed to investigate the beneficial effect of PEA administration in counteracting the enteric inflammation and relieving the bowel motor dysfunctions in an AD mouse model, SAMP8 mice. In addition, the ability of PEA in modulating the activation of enteric glial cells (EGCs), pivotally involved in the pathophysiology of bowel dysfunctions associated with inflammatory conditions, has also been examined. SAMP8 mice at 4 months of age were treated orally with PEA (5 mg/kg/day) for 2 months. SAMR1 animals were employed as controls. At the end of treatment, parameters dealing with colonic motility, inflammation, barrier integrity and AD protein accumulation were evaluated. The effect of PEA on EGCs was tested in cultured cells treated with lipopolysaccharide (LPS) plus β-amyloid 1–42 (Aβ). SAMP8 treated with PEA displayed: 1) an improvement of in vitro colonic motor activity, citrate synthase activity and intestinal epithelial barrier integrity and 2) a decrease in colonic Aβ and α-synuclein (α-syn) accumulation, S100-β expression as well as enteric IL-1β and circulating LPS levels, as compared with untreated SAMP8 mice. In EGCs, treatment with PEA counteracted the increment of S100-β, TLR-4, NF-κB p65 and IL-1β release induced by LPS and Aβ. These results suggest that PEA, under a condition of cognitive decline, prevents the enteric glial hyperactivation, reduces AD protein accumulation and counteracts the onset and progression of colonic inflammatory condition, as well as relieves intestinal motor dysfunctions and improves the intestinal epithelial barrier integrity. Therefore, PEA represents a viable approach for the management of the enteric inflammation and motor contractile abnormalities associated with AD.https://www.frontiersin.org/articles/10.3389/fphar.2021.748021/fullalzheimer’s diseasecolonic dysmotilityenteric glial cellsenteric gliosisintestinal inflammationpalmitoylethanolamide |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vanessa D’Antongiovanni Carolina Pellegrini Luca Antonioli Laura Benvenuti Clelia Di Salvo Lorenzo Flori Rebecca Piccarducci Simona Daniele Alma Martelli Alma Martelli Alma Martelli Vincenzo Calderone Vincenzo Calderone Vincenzo Calderone Claudia Martini Matteo Fornai |
spellingShingle |
Vanessa D’Antongiovanni Carolina Pellegrini Luca Antonioli Laura Benvenuti Clelia Di Salvo Lorenzo Flori Rebecca Piccarducci Simona Daniele Alma Martelli Alma Martelli Alma Martelli Vincenzo Calderone Vincenzo Calderone Vincenzo Calderone Claudia Martini Matteo Fornai Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease Frontiers in Pharmacology alzheimer’s disease colonic dysmotility enteric glial cells enteric gliosis intestinal inflammation palmitoylethanolamide |
author_facet |
Vanessa D’Antongiovanni Carolina Pellegrini Luca Antonioli Laura Benvenuti Clelia Di Salvo Lorenzo Flori Rebecca Piccarducci Simona Daniele Alma Martelli Alma Martelli Alma Martelli Vincenzo Calderone Vincenzo Calderone Vincenzo Calderone Claudia Martini Matteo Fornai |
author_sort |
Vanessa D’Antongiovanni |
title |
Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease |
title_short |
Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease |
title_full |
Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease |
title_fullStr |
Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease |
title_full_unstemmed |
Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease |
title_sort |
palmitoylethanolamide counteracts enteric inflammation and bowel motor dysfunctions in a mouse model of alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-09-01 |
description |
Palmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer’s disease (AD) are lacking. This study was designed to investigate the beneficial effect of PEA administration in counteracting the enteric inflammation and relieving the bowel motor dysfunctions in an AD mouse model, SAMP8 mice. In addition, the ability of PEA in modulating the activation of enteric glial cells (EGCs), pivotally involved in the pathophysiology of bowel dysfunctions associated with inflammatory conditions, has also been examined. SAMP8 mice at 4 months of age were treated orally with PEA (5 mg/kg/day) for 2 months. SAMR1 animals were employed as controls. At the end of treatment, parameters dealing with colonic motility, inflammation, barrier integrity and AD protein accumulation were evaluated. The effect of PEA on EGCs was tested in cultured cells treated with lipopolysaccharide (LPS) plus β-amyloid 1–42 (Aβ). SAMP8 treated with PEA displayed: 1) an improvement of in vitro colonic motor activity, citrate synthase activity and intestinal epithelial barrier integrity and 2) a decrease in colonic Aβ and α-synuclein (α-syn) accumulation, S100-β expression as well as enteric IL-1β and circulating LPS levels, as compared with untreated SAMP8 mice. In EGCs, treatment with PEA counteracted the increment of S100-β, TLR-4, NF-κB p65 and IL-1β release induced by LPS and Aβ. These results suggest that PEA, under a condition of cognitive decline, prevents the enteric glial hyperactivation, reduces AD protein accumulation and counteracts the onset and progression of colonic inflammatory condition, as well as relieves intestinal motor dysfunctions and improves the intestinal epithelial barrier integrity. Therefore, PEA represents a viable approach for the management of the enteric inflammation and motor contractile abnormalities associated with AD. |
topic |
alzheimer’s disease colonic dysmotility enteric glial cells enteric gliosis intestinal inflammation palmitoylethanolamide |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.748021/full |
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