Repurposing beta-3 adrenergic receptor agonists for Alzheimer’s disease: beneficial effects in a mouse model
| العنوان: | Repurposing beta-3 adrenergic receptor agonists for Alzheimer’s disease: beneficial effects in a mouse model |
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| المؤلفون: | Tra-My Vu, Nika Vrabic, Clara Hozer, Emmanuel Planel, Frédéric Calon, Cyntia Tremblay, Marine Tournissac, Koralie Melancon, Fabien Pifferi |
| المساهمون: | Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-17 (2021) Alzheimer's Research and Therapy Alzheimer's Research and Therapy, BioMed Central, 2021, 13, ⟨10.1186/s13195-021-00842-3⟩ Alzheimer's Research & Therapy |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, Beta-3 adrenergic receptor, Genetically modified mouse, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Cognitive Neuroscience, Drug repurposing, Hippocampus, Mice, Transgenic, tau Proteins, Stimulation, Neurosciences. Biological psychiatry. Neuropsychiatry, Brown adipose tissue, Mice, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Cold acclimation, Animals, 3xTg-AD mice, β3 adrenergic receptors, RC346-429, Amyloid beta-Peptides, business.industry, Research, Thermogenesis, Alzheimer's disease, Adrenergic Agonists, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Neurology, Neurology (clinical), Neurology. Diseases of the nervous system, business, Alzheimer’s disease, 030217 neurology & neurosurgery, RC321-571 |
| الوصف: | Background Old age, the most important risk factor for Alzheimer’s disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well. Methods CL-316,243, a specific β3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p. Results Here, we show that β3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice. Conclusions Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy. |
| اللغة: | English |
| تدمد: | 1758-9193 |
| DOI: | 10.1186/s13195-021-00842-3⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ddc377b321107aefe00215ec9910cc9 https://doaj.org/article/3f8e713fbb2149919411a3edf8de6511 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2ddc377b321107aefe00215ec9910cc9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17589193 |
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| DOI: | 10.1186/s13195-021-00842-3⟩ |