IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function

PARDO, JOAQUÍN; ABBA, MARTIN C.; OGUNDELE, OLALEKAN M.; PAIVA, ISABEL; OUTEIRO, TIAGO F.; GOYA, RODOLFO G.; ABBA, MARTIN C.; LACUNZA, EZEQUIEL; PAIVA, ISABEL; MOREL, GUSTAVO R.; LACUNZA, EZEQUIEL; GOYA, RODOLFO G.; MOREL, GUSTAVO R.; PARDO, JOAQUÍN; OGUNDELE, OLALEKAN M.; OUTEIRO, TIAGO F.

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

GERONTOLOGICAL SOC AMER

Año: 2018 vol. 14 p. 459 - 467

1079-5006

In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28 months old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.