title: WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture.
abstract: Alzheimer's disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death. Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD. However, studies on the effects of cannabinoids on astrocytes functions are scarce. In primary cultured astrocytes we studied cellular viability using MTT assay. Inflammatory and oxidative stress mediators were determined by ELISA and Western-blot techniques both in the presence and absence of Aβ1-42 peptide. Effects of WIN 55,212-2 (a synthetic cannabinoid) on cell viability, inflammatory mediators and oxidative stress were also determined. Aβ1-42 diminished astrocytes viability, increased TNF-α and IL-1β levels and p-65, COX-2 and iNOS protein expression while decreased PPAR-γ and antioxidant enzyme Cu/Zn SOD. WIN 55,212-2 pretreatment prevents all effects elicited by Aβ1-42. Furthermore, cannabinoid WIN 55,212-2 also increased cell viability and PPAR-γ expression in control astrocytes. In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes. Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer's disease patients.
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Diana
authors: D
authors: Aguirre-Rueda
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Sol
authors: S
authors: Guerra-Ojeda
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Martin
authors: M
authors: Aldasoro
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Antonio
authors: A
authors: Iradi
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Elena
authors: E
authors: Obrador
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Maria D
authors: MD
authors: Mauricio
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Jose M
authors: JM
authors: Vila
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Patricia
authors: P
authors: Marchio
authors: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors: Soraya L
authors: SL
authors: Valles
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048588:Benzoxazines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D043882:Receptors, Cannabinoid / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D063386:Cannabinoid Receptor Agonists; D053583:Interleukin-1beta; D009025:Morpholines; D009281:Naphthalenes; D047495:PPAR gamma; D010446:Peptide Fragments; D043882:Receptors, Cannabinoid; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase