دورية أكاديمية
Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer’s Disease Mouse Model
| العنوان: | Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer’s Disease Mouse Model |
|---|---|
| المؤلفون: | Zamarbide, Marta, Martínez Pinilla, Eva, Gil Bea, Francisco, Yanagisawa, Masashi, Franco, Rafael, Pérez Mediavilla, Alberto |
| سنة النشر: | 2024 |
| المجموعة: | Universidad de Oviedo: RUO |
| مصطلحات موضوعية: | Alzheimer’s disease, Neuroprotection, Therapy, Synaptic plasticity, Learning and memory, Amyloid |
| الوصف: | The free fatty acid FFA3 receptor (FFA3R) belongs to the superfamily of G-protein-coupled receptors (GPCRs). In the intestine and adipose tissue, it is involved in the regulation of energy metabolism, but its function in the brain is unknown. We aimed, first, to investigate the expression of the receptor in the hippocampus of Alzheimer disease (AD) patients at different stages of the disease and, second, to assess whether genetic inactivation of the Ffar3 gene could affect the phenotypic features of the APPswe mouse model. The expression of transcripts for FFA receptors in postmortem human hippocampal samples and in the hippocampus of wild-type and transgenic mice was analyzed by RT-qPCR.We generated a double transgenic mouse, FFA3R//APPswe, to perform cognition studies and to assess, by immunoblotting A and tau pathologies and the differential expression of synaptic plasticity-related proteins. For the first time, the occurrence of the FFA3R in the human hippocampus and its overexpression, even in the first stages of AD, was demonstrated. Remarkably, FFA3R//APPswe mice do not have the characteristic memory impairment of 12-month-old APPswe mice. Additionally, this newly generated transgenic line does not develop the most important Alzheimer’s disease (AD)-related features, such as amyloid beta (A ) brain accumulations and tau hyperphosphorylation. These findings are accompanied by increased levels of the insulin-degrading enzyme (IDE) and lower activity of the tau kinases GSK3 and Cdk5. We conclude that the brain FFA3R is involved in cognitive processes and that its inactivation prevents AD-like cognitive decline and pathological hallmarks. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | International Journal of Molecular Sciences; Foundation for Applied Medical Research (FIMA) intramural funds. M.Z. was funded by The Asociación de Amigos de la Universidad de Navarra; https://doi.org/10.3390/ijms23073533Test; International Journal of Molecular Sciences, 23(7):3533 (2022); doi:10.3390/ijms23073533; https://hdl.handle.net/10651/70567Test |
| الإتاحة: | https://doi.org/10.3390/ijms23073533Test https://hdl.handle.net/10651/70567Test |
| حقوق: | CC Reconocimiento 4.0 Internacional ; © 2022 by the authors. ; http://creativecommons.org/licenses/by/4.0Test/ ; open access |
| رقم الانضمام: | edsbas.B755EFA8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |