Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer's disease in metabolically stressed APPswe/PS1dE9 mice

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Ettcheto, Miren ^{[1, 2, 3, 4]} ; Sanchez-Lopez, Elena ^{[1, 5, 6]} ; Cano, Amanda ^{[1, 5, 6, 7]} ; Carrasco, Marina ^{[1, 2, 3, 8]} ; Herrera, Katherine ^{[3, 9]} ; Manzine, Patricia R. ^[10] ; Espinosa-Jimenez, Triana ^{[1, 2, 3]} ; Busquets, Oriol ^[11] ; Verdaguer, Ester ^{[1, 3, 9]} ; Olloquequi, Jordi ^[12] ; Auladell, Carme ^{[1, 3, 9]} ; Folch, Jaume ^{[1, 8]} ; Camins, Antoni ^{[1, 2, 3]}

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^[1] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid - Spain

^[2] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona - Spain

^[3] Univ Barcelona, Inst Neurosci, Barcelona - Spain

^[4] Univ Barcelona, Unitat Farmacol & Farmacognosia, Fac Farm & Ciencies Alimentacio, Av Joan XXIII 27-31, Barcelona 08028 - Spain

^[5] Univ Barcelona, Inst Nanosci & Nanotechnol IN2UB, Barcelona - Spain

^[6] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm, Pharmaceut Technol & Phys Chem, Barcelona - Spain

^[7] Int Univ Catalunya UIC, Res Ctr & Memory Clin, Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona - Spain

^[8] Univ Rovira & Vrgili, Dept Biochem & Biotechnol, Fac Med & Life Sci, Reus - Spain

^[9] Univ Barcelona, Dept Cellular Biol Physiol & Immunol, Fac Biol, Barcelona - Spain

^[10] Fed Univ Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos - Brazil

^[11] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, New York, NY 10461 - USA

^[12] Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Lab Cellular & Mol Pathol, Talca - Chile

• Tipo de documento: Artigo Científico
• Fonte: CELL AND BIOSCIENCE; v. 11, n. 1 JUL 22 2021.
• Citações Web of Science: 0

Resumo

Background Several studies stablished a relationship between metabolic disturbances and Alzheimer ` s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg(-1) d(-1)) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. (AU)

• Processo FAPESP: 17/13224-5 - Estudo da via JNK1 como alvo seletivo para o tratamento de transtorno metabólico cognitivo: análise da proteína ADAM10
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/26084-1 - Avaliação da ADAM10 plaquetária em demências não-Alzheimer
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado