info:eu-repo/semantics/article
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
Fecha
2019-11-23Registro en:
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
0893-7648
CONICET Digital
CONICET
Autor
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
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.