title: Differential Effects of Palmitoylethanolamide against Amyloid-β Induced Toxicity in Cortical Neuronal and Astrocytic Primary Cultures from Wild-Type and 3xTg-AD Mice.
abstract: BACKGROUND
  Considering the heterogeneity of pathological changes occurring in Alzheimer's disease (AD), a therapeutic approach aimed both to neuroprotection and to neuroinflammation reduction may prove effective. Palmitoylethanolamide (PEA) has attracted attention for its anti-inflammatory/neuroprotective properties observed in AD animal models.
  
  
  OBJECTIVE
  We evaluated the protective role of PEA against amyloid-β₄₂ (Aβ₄₂) toxicity on cell viability and glutamatergic transmission in primary cultures of cerebral cortex neurons and astrocytes from the triple-transgenic murine model of AD (3xTg-AD) and their wild-type littermates (non-Tg) mice.
  
  
  RESULTS
  Aβ₄₂ (0.5 μM; 24 h) affects the cell viability in cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. These effects were counteracted by the pretreatment with PEA (0.1 μM). Basal glutamate levels in cultured neurons and astrocytes from 3xTg-AD mice were lower than those observed in cultured cells from non-Tg mice. Aβ₄₂-exposure reduced and increased glutamate levels in non-Tg mouse cortical neurons and astrocytes, respectively. These effects were counteracted by the pretreatment with PEA. By itself, PEA did not affect cell viability and glutamate levels in cultured cortical neurons and astrocytes from non-Tg or 3xTg-AD mice.
  
  
  CONCLUSIONS
  The exposure to Aβ₄₂ induced toxic effects on cultured cortical neurons and astrocytes from non-Tg mice, but not in those from 3xTg-AD mice. Furthermore, PEA exerts differential effects against Aβ₄₂-induced toxicity in primary cultures of cortical neurons and astrocytes from non-Tg and 3xTg-AD mice. In particular, PEA displays protective properties in non-Tg but not in 3xTg-AD mouse neuronal cultured cells overexpressing Aβ.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Tomasini
authors.affiliation: Department of Medical Sciences, University of Ferrara, Italy.
authors.forename: Andrea Celeste
authors.initials: AC
authors.lastname: Borelli
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beggiato
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.|LTTA Centre, University of Ferrara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.affiliation: IRET Foundation, Ozzano Emilia, Bologna, Italy.|Department of Medical Sciences, University of Ferrara, Italy.|LTTA Centre, University of Ferrara, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tanganelli
authors.affiliation: IRET Foundation, Ozzano Emilia, Bologna, Italy.|Department of Medical Sciences, University of Ferrara, Italy.|LTTA Centre, University of Ferrara, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000577:Amides; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000494:pharmacology*; D018698:Glutamic Acid / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects*; D010169:Palmitic Acids / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004983:Ethanolamines; D010169:Palmitic Acids; D016875:tau Proteins; D018698:Glutamic Acid; C005958:palmidrol
keywords: Alzheimer’s disease; GFAP immunoreactivity; MAP2 immunoreactivity; cell viability; glutamate