Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of Aβ Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model
| العنوان: | Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of Aβ Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model |
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| المؤلفون: | Juliana T.S. Fortuna, Sergio T. Ferreira, Claudia K. Suemoto, Renata Elaine Paraizo Leite, Paula C. Reggiani, Maria Clara Selles, Roberta Diehl Rodriguez, Lea T. Grinberg, Amanda Santos de Souza, Yasmin P R de Faria, Maria F. Zappa-Villar |
| المصدر: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Mol Neurobiol Molecular neurobiology, vol 57, iss 3 |
| بيانات النشر: | Humana Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Aging, Dendritic spine, Hippocampal formation, Neurodegenerative, medicine.disease_cause, Alzheimer's Disease, Hippocampus, Synapse, Mice, 0302 clinical medicine, 80 and over, 2.1 Biological and endogenous factors, Psychology, Aetiology, Insulin-Like Growth Factor I, Aged, 80 and over, Neurons, biology, DEMENTIA, Human brain, purl.org/becyt/ford/3.1 [https], HUMAN BRAIN, Cell biology, medicine.anatomical_structure, Neurology, Neurological, Cognitive Sciences, Female, purl.org/becyt/ford/3 [https], hormones, hormone substitutes, and hormone antagonists, endocrine system, Neuroscience (miscellaneous), Neuroprotection, Article, Adenoviridae, ADENOVIRUS, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, Memory, medicine, Acquired Cognitive Impairment, Animals, Humans, Insulin-like growth factor 1 receptor, Aged, Memory Disorders, Neurology & Neurosurgery, Amyloid beta-Peptides, Animal, Prevention, INSULIN-LIKE GROWTH FACTOR I, MEMORY, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Insulin receptor, Disease Models, Animal, 030104 developmental biology, Disease Models, Synapses, biology.protein, HIPPOCAMPUS, 030217 neurology & neurosurgery, Oxidative stress |
| الوصف: | Alzheimer´s disease (AD) is the main cause of dementia in the elderly. Although activation of brain insulin signaling has been shown to be neuroprotective, to preserve memory in AD models, and appears beneficial in patients, the role of insulin-like growth factor 1 (IGF1) remains incompletely understood. We found reduced active/inactive IGF1 ratio and increased IGF1R expression in postmortem hippocampal tissue from AD patients, suggesting impaired brain IGF1 signaling in AD. Active/inactive IGF-1 ratio was also reduced in the brains of mouse models of AD. We next investigated the possible protective role of IGF1 in AD models. We used a recombinant adenoviral vector, RAd-IGF1, to drive the expression of IGF1 in primary hippocampal neuronal cultures prior to exposure to AβOs, toxins that accumulate in AD brains and have been implicated in early synapse dysfunction and memory impairment. Cultures transduced with RAd-IGF1 showed decreased binding of AβOs to neurons and were protected against AβO-induced neuronal oxidative stress and loss of dendritic spines. Significantly, in vivo transduction with RAd-IGF1 blocked memory impairment caused by intracerebroventricular (i.c.v.) infusion of AβOs in mice. Our results demonstrate altered active IGF1 and IGF1R levels in AD hippocampi, and suggest that boosting brain expression of IGF1 may comprise an approach to prevent neuronal damage and memory loss in AD. Fil: Selles, Maria Clara. Universidade Federal do Rio de Janeiro; Brasil Fil: Fortuna, Juliana T. S.. Universidade Federal do Rio de Janeiro; Brasil Fil: Zappa Villar, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: de Faria, Yasmin P. R.. Universidade Federal de Sao Paulo; Brasil Fil: Souza, Amanda S.. Universidade Federal do Rio de Janeiro; Brasil Fil: Suemoto, Claudia K.. Universidade Federal de Sao Paulo; Brasil Fil: Leite, Renata E. P.. Universidade Federal de Sao Paulo; Brasil Fil: Rodriguez, Roberta D.. Universidade Federal de Sao Paulo; Brasil Fil: Grinberg, Lea T.. Universidade Federal de Sao Paulo; Brasil. University of California; Estados Unidos Fil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Ferreira, Sergio Teixeira. Universidade Federal do Rio de Janeiro; Brasil |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::472eaf9dd8a911a05bc85753379cd504Test http://link.springer.com/10.1007/s12035-019-01827-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....472eaf9dd8a911a05bc85753379cd504 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |