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Title: Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of A beta Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model
Authors: SELLES, Maria ClaraFORTUNA, Juliana T. S.ZAPPA-VILLAR, Maria F.FARIA, Yasmin P. R. deSOUZA, Amanda S.SUEMOTO, Claudia K.LEITE, Renata E. P.RODRIGUEZ, Roberta D.GRINBERG, Lea T.REGGIANI, Paula C.FERREIRA, Sergio T.
Citation: MOLECULAR NEUROBIOLOGY, v.57, n.3, p.1473-1483, 2020
Abstract: 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 A beta Os, 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 A beta Os to neurons and were protected against A beta O-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 A beta Os 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.
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Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - LIM/22
LIM/22 - Laboratório de Patolologia Cardiovascular

Artigos e Materiais de Revistas Científicas - LIM/66
LIM/66 - Laboratório de Investigação Médica em Envelhecimento

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