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

CÓNSOLE GM; MOREL GR; PARDO J; REGGIANI PC; GOYA RG; URIARTE M; OUTEIRO TF

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 p. 1 - 9

0953-816X

In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluatetherapeutic strategies of potential value for correcting age-related cognitive deficits. Some of these strategies involve neurotrophicfactors like insulin-like growth factor-I (IGF-I), a powerful neuroprotective molecule in the brain. Here, we implemented 18-daylong intracerebroventricular (ICV) IGF-I gene therapy in 28 months old Sprague?Dawley female rats, and assessed spatial memoryperformance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectorsexpressing the gene for rat IGF-I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken andIGF-I levels determined by radioimmunoassay. At the end of the study, IGF-I levels in the CSF were significantly higher in theexperimental group than in the DsRed controls. After treatment, the IGF-I group showed a significant improvement in spatialmemory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF-I group showeda higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching andreduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach toincrease CSF levels of IGF-I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect ofthe treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performancein aging rats.