Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a Mixed Model of Alzheimer’s Disease and Type 2 Diabetes
| Autor: | Juan Jose Ramos-Rodriguez, Eleanor K. Pickett, Rosemary J. Jackson, Esperanza Ortegon, Carmen Infante-Garcia, Tara L. Spires-Jones, Fernando Hernandez-Pacho, Carmen Hierro-Bujalance, Monica Garcia-Alloza |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Neurology endocrine system diseases Type 2 diabetes Bioinformatics 0302 clinical medicine Phosphorylation Polypill Neurons Aspirin biology Brain Lipids 3. Good health Metformin Amyloid-beta Alzheimer’s disease medicine.drug medicine.medical_specialty Amyloid Amyloid beta Neuroscience (miscellaneous) Hemorrhage Mice Transgenic tau Proteins 03 medical and health sciences Cellular and Molecular Neuroscience Atrophy Alzheimer Disease medicine Dementia Animals Humans Hypoglycemic Agents Cognitive Dysfunction Cerebral Hemorrhage Inflammation Amyloid beta-Peptides business.industry nutritional and metabolic diseases medicine.disease Disease Models Animal 030104 developmental biology Diabetes Mellitus Type 2 Synapses biology.protein Polypharmacy Tau business 030217 neurology & neurosurgery |
| Zdroj: | Molecular Neurobiology Infante-Garcia, C, Ramos-Rodriguez, J J, Hierro-Bujalance, C, Ortegon, S, Pickett, E, Jackson, R, Hernandez-Pacho, F, Spires-Jones, T & Garcia-Alloza, M 2017, ' Antidiabetic polypill improves central pathology and cognitive impairment in a mixed model of Alzheimer's disease and type 2 diabetes ', Molecular Neurobiology . https://doi.org/10.1007/s12035-017-0825-7 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-017-0825-7 |
| Popis: | Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor. In order to test the effects of PP at the central level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db mouse. We have analyzed AD pathological features and the underlying specific characteristics that relate AD and T2D. As expected, metabolic alterations were ameliorated after PP treatment in diabetic mice, supporting a role for PP in maintaining pancreatic activity. At central level, PP reduced T2D-associated brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid pathologies were also reduced after PP treatment. Furthermore, we observed a reduction of spontaneous central bleeding and inflammation after PP treatment in diabetic mice. As consequence, learning and memory processes were improved after PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further analyze the role of PP, as an alternative or adjuvant, to slow down or delay the central complications associated with T2D and AD. |
| Databáze: | OpenAIRE |
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