SIRT1 overexpression in mouse hippocampus induces cognitive enhancement through proteostatic and neurotrophic mechanisms
| Autor: | Marco Castro-Freire, Valérie Petegnief, Susana Revilla, Perla Kaliman, Mercè Pallàs, Lydia Giménez-Llort, Coral Sanfeliu, Rubén Corpas, Chamsy Sarkis, Suzanna Ursulet |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Sanfeliu, Coral, Sanfeliu, Coral [0000-0002-9004-1206] |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Amyloid Neuroscience (miscellaneous) Hippocampus Mice Transgenic Hippocampal formation Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience Amyloid beta-Protein Precursor 0302 clinical medicine Cognition SIRT1 Sirtuin 1 Neurotrophic factors medicine Glial cell line-derived neurotrophic factor Animals Learning 3xTg-AD mice Nootropic Agents Neurons biology Proteasome Insulin-degrading enzyme (IDE) Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology biology.protein Neuron Neuroscience 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists Glial cell line-derived neurotrophic factor (GDNF) Neurotrophin Cognitive enhancement |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | SIRT1 induces cell survival and has shown neuroprotection against amyloid and tau pathologies in Alzheimer’s disease (AD). However, protective effects against memory loss or the enhancement of cognitive functions have not yet been proven. We aimed to investigate the benefits induced by SIRT1 overexpression in the hippocampus of the AD mouse model 3xTg-AD and in control non-transgenic mice. A lentiviral vector encoding mouse SIRT1 or GFP, selectively transducing neurons, was injected into the dorsal CA1 hippocampal area of 4-month-old mice. Six-month overexpression of SIRT1 fully preserved learning and memory in 10-month-old 3xTg-AD mice. Remarkably, SIRT1 also induced cognitive enhancement in healthy non-transgenic mice. Neuron cultures of 3xTg-AD mice, which show traits of AD-like pathology, and neuron cultures from non-transgenic mice were also transduced with lentiviral vectors to analyze beneficial SIRT1 mechanisms. We uncovered novel pathways of SIRT1 neuroprotection through enhancement of cell proteostatic mechanisms and activation of neurotrophic factors not previously reported such as GDNF, present in both AD-like and healthy neurons. Therefore, SIRT1 may increase neuron function and resilience against AD. This study was supported by Grants CSD2010- 00045 and SAF2012-39852 from the Spanish Ministry of Economy and Competitiveness (MINECO) and the European Regional Development Fund (ERDF). |
| Databáze: | OpenAIRE |
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