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

• Published in: Cell & bioscience Vol. 11; no. 1; pp. 141 - 17
• Main Authors: Ettcheto, Miren, Sánchez-Lopez, Elena, Cano, Amanda, Carrasco, Marina, Herrera, Katherine, Manzine, Patricia R, Espinosa-Jimenez, Triana, Busquets, Oriol, Verdaguer, Ester, Olloquequi, Jordi, Auladell, Carme, Folch, Jaume, Camins, Antoni
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22-07-2021; BioMed Central; BMC
• Subjects: Advertising executives; Alzheimer's disease; Alzheimer´s disease; Animal genetic engineering; Anti-inflammatory agents; APPswe/PS1dE9; Body weight; Brain; Cognitive ability; Dexibuprofen; Dextrose; Diabetes; Drinking water; Drug dosages; Genetically modified animals; Glucose; Glucose tolerance; Glucose tolerance tests; High fat diet; Hypotheses; Inflammation; Insulin; Insulin resistance; Liver; Memory; Metabolic disorders; Neurodegenerative diseases; neuroinflammation; Nonsteroidal anti-inflammatory drugs; Pathology; Polymerase chain reaction; Presenilin 1; Protein folding; Proteins; Risk factors; Software; Synapsis; Transgenic animals; Type 2 diabetes; Unfolded protein response; Weaning; β-Amyloid; United States > US; Germany; Synapsis; Alzheimer´s disease; neuroinflammation; Dexibuprofen; Metabolic alterations; Cognitive deficits; βA plaques; APPswe/PS1dE9; High fat diet; Unfolded protein response
• ISSN: 2045-3701; 2045-3701
• DOI: 10.1186/s13578-021-00646-w

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
 d
) 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.
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.
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.