CONICET | Buscador de Institutos y Recursos Humanos

In the last decades, the average lifespan has increased due to the improvement on medical care and social and cultural conditions. This fact comes together with the consequent motor and cognitive impairment as well as an increment in the incidence of age-related pathologies, such as Parkinson?s disease. Aging presents a loss of brain homeostasis and a chronic neuroinflammation, caused by senescent microglia, which are polarized towards a pro-inflammatory phenotype, generating thus an exacerbated immune response. In fact, the progression of many neurodegenerative diseases is dependent on microglia activation.Therefore, it is of great interest to design strategies that allow modulating these glial cells phenotype. One possibility to modulate microglia activation in the aged brain is the use of neurotrophic factors. Many neurotrophic factors produced by glial cells, such as IGF1, are able to polarize them into a more neurotrophic/neuroprotective phenotype, promoting neuronal survival. Therefore, we implemented IGF1 gene therapy in aged rats and studied who the motor improvement (previously observed in our laboratory) and microglia activation could be related. We demonstrated that the therapy modulated microglia number and activation in an area-dependent manner. Moreover, IGF1-therapy efficiently polarized microglia in the Striatum into an anti-inflammatory phenotype. Finally, IGF1 increased microglial phagocytic activity in the Striatum, promoting the elimination of neurons expression Homer1. These results suggest that IGF1 gene therapy could be an effective treatment to modulate microglia activation and promote motor improvement.