Intracerebroventricular IGF-I gene therapy for cognitive deficit in the senile rat

PARDO J; MOREL, G.R.; REGGIANI PC; HEREÑÚ CB; GOYA RG

Congreso; 8th Annual Canadian Neuroscience Meeting 2014; 2014

Ageing plays a key role in the development ofneurodegenerative disorders. Although there isa substantial number of studies addressing thechanges in the brain of old rats (24 mo), there isscarce information about neurological deficits invery old rats (28 mo or older). The use ofneurotrophic factors, such as IGF-I, is emergingas a promising therapeutic tool to prevent neuraldamage and restore the function of theremaining population of neurons. In order to gather more information on the age-relatedchanges in very old rats, we undertook a studyin 28 month-old female rats. A set of senile ratsreceived an icv stereotaxic injection of either thetherapeutic adenovector RAd-IGF-I, expressingthe gene for IGF-I (experimental group) or thecontrol adenovector RAd-DsRed2, expressingthe gene for the red fluorescent protein. Bothgroups were tested in the Barnes Maze.Interestingly, the experimental group showedsome improvement in spatial memory, whereasthe control group displayed a poorerperformance. Also, immunohistochemistrystudies showed that the experimental group hada higher rate of neurogenesis in the DentateGyrus than the control counterparts. Also, theexperimental animals showed less astrogliosisin the stratum radiatum of the hippocampus thanthe control group. These results suggest thatshort-term IGF-I gene therapy can amelioratesome age-associated functional andmorphological deficits in rats and encourage usto undertake a long-term study, in order toassess the preventive capability of IGF-I genetherapy when the treatment is started at anearlier age