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Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats

Lookup NU author(s): Professor Tiago OuteiroORCiD


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© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age-related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin-like growth factor-I (IGF-I), a powerful neuroprotective molecule in the brain. Here, we implemented 18-day long intracerebroventricular (ICV) IGF-I gene therapy in 28 months old Sprague–Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF-I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF-I levels determined by radioimmunoassay. At the end of the study, IGF-I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF-I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF-I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF-I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats.

Publication metadata

Author(s): Pardo J, Uriarte M, Console GM, Reggiani PC, Outeiro TF, Morel GR, Goya RG

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2016

Volume: 44

Issue: 4

Pages: 2120-2128

Print publication date: 01/08/2016

Online publication date: 18/05/2016

Acceptance date: 10/05/2016

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell


DOI: 10.1111/ejn.13278

PubMed id: 27188415


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