IGF-I gene therapy in aging rats modulates hippocampal genes relevant to memory 
function

Pardo, Joaquín; Abba , Martin C.; Lacunza, Ezequiel; Ogundele, Olalekan M.; Paiva, Isabel; Morel, Gustavo R.; Outeiro, Tiago F.; Goya, Rodolfo G.

doi:10.1093/gerona/glx125

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IGF-I gene therapy in aging rats modulates hippocampal genes relevant to memory function

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Outeiro, Tiago F.
Experimental Neurodegeneration, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Pardo, J., Abba, M. C., Lacunza, E., Ogundele, O. M., Paiva, I., Morel, G. R., et al. (2017). IGF-I gene therapy in aging rats modulates hippocampal genes relevant to memory function. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences, 73(4), 459-467. doi:10.1093/gerona/glx125.

Cite as: https://hdl.handle.net/21.11116/0000-0003-23FB-B

Abstract

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-month-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.