Autor(es):
Duarte, Ana I. ; Candeias, Emanuel ; Alves, Inês ; Mena, Débora ; Silva, Daniela F. ; Machado, Nuno J. ; Campos, Elisa J. ; Santos, Maria S. ; Oliveira, Catarina R. ; Moreira, Paula I.
Data: 2020
Identificador Persistente: https://hdl.handle.net/10316/106194
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): Alzheimer’s disease; brain protection; female sex; GLP-1 mimetics; liraglutide; Alzheimer Disease; Amyloid beta-Peptides; Animals; Behavior, Animal; Brain; Cyclic AMP-Dependent Protein Kinases; Diabetes Mellitus, Type 2; Estradiol; Female; Glucagon-Like Peptide 1; Glycolysis; Hypoglycemic Agents; Inflammation; Liraglutide; Maze Learning; Memory Disorders; Mice; Neurofibrillary Tangles; Nitrosative Stress; Oxidative Stress; Peptide Fragments; Phenotype; Plaque, Amyloid
Descrição
Alzheimer's disease (AD) is the most common form of dementia worldwide, being characterized by the deposition of senile plaques, neurofibrillary tangles (enriched in the amyloid beta (Aβ) peptide and hyperphosphorylated tau (p-tau), respectively) and memory loss. Aging, type 2 diabetes (T2D) and female sex (especially after menopause) are risk factors for AD, but their crosslinking mechanisms remain unclear. Most clinical trials targeting AD neuropathology failed and it remains incurable. However, evidence suggests that effective anti-T2D drugs, such as the GLP-1 mimetic and neuroprotector liraglutide, can be also efficient against AD. Thus, we aimed to study the benefits of a peripheral liraglutide treatment in AD female mice. We used blood and brain cortical lysates from 10-month-old 3xTg-AD female mice, treated for 28 days with liraglutide (0.2 mg/kg, once/day) to evaluate parameters affected in AD (e.g., Aβ and p-tau, motor and cognitive function, glucose metabolism, inflammation and oxidative/nitrosative stress). Despite the limited signs of cognitive changes in mature female mice, liraglutide only reduced their cortical Aβ1-42 levels. Liraglutide partially attenuated brain estradiol and GLP-1 and activated PKA levels, oxidative/nitrosative stress and inflammation in these AD female mice. Our results support the earlier use of liraglutide as a potential preventive/therapeutic agent against the accumulation of the first neuropathological features of AD in females.
This work was supported by the European Regional Development Fund (EDRF), through the Centro 2020 Regional Operational Programme (Projects Healthy Aging2020, Centro-01-0145-FEDER-000012; PTDC/SAU-TOX/117481/2010); by COMPETE 2020 (Operational Programme for Competitiveness and Internationalization); by Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (projects: PTDC/SAUTOX/117481/2010; UIDB/NEU/04539/2020; and by the European Social Fund (Fellowship SFRH/BD/90036/2012 to E. Candeias and Post-Doctoral Researcher Contract DL57/2016 #SFRH/BPD/84473/2012 to A. I. Duarte).
