Artículo
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
Selles, Maria Clara; Fortuna, Juliana T. S.; Zappa Villar, María Florencia
; de Faria, Yasmin P. R.; Souza, Amanda S.; Suemoto, Claudia K.; Leite, Renata E. P.; Rodriguez, Roberta D.; Grinberg, Lea T.; Reggiani, Paula Cecilia
; Ferreira, Sergio Teixeira


Fecha de publicación:
23/11/2019
Editorial:
Humana Press
Revista:
Molecular Neurobiology
ISSN:
0893-7648
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
ADENOVIRUS
,
DEMENTIA
,
HIPPOCAMPUS
,
HUMAN BRAIN
,
INSULIN-LIKE GROWTH FACTOR I
,
MEMORY
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Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Selles, Maria Clara; Fortuna, Juliana T. S.; Zappa Villar, María Florencia; de Faria, Yasmin P. R.; Souza, Amanda S.; et al.; 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; Humana Press; Molecular Neurobiology; 57; 3; 23-11-2019; 1473-1483
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