CONICET | Buscador de Institutos y Recursos Humanos

The increase in average life expectancy is accompanied by an increment in the incidence of degenerative diseases associated with age. A typical characteristic of both aging and neurodegenerative diseases is a chronic inflammation mediated by glial cells. As a consequence, there is a marked rise in the production of pro-inflammatory cytokines and inflammation markers. Many studies have demonstrated that neuroinflammation mediated by microglia and astroglia plays a key role in neuronal survival as well as in death. Furthermore, an adequate regulation of neuroinflammation is essential to prevent the progression of neurodegenerative diseases. A possible approach to control neuroinflammation is the use of neurotrophic factors. Among this, IGF1 is well known by its neuroprotective role in the CNS. Moreover, our group has previously described that ICV IGF-1 gene therapy induced a significant improvement in motor performance in aged rats. Regarding this, we propose that restorative effects of IGF-1 in motor skills could be mediated by glial cells.In this project, we implemented ICV IGF-1 neuroprotective gene therapy in two rat models: the brain of senile rats (28 mounth-old) and a rat model of Parkinson?s disease induced by nigral injection of LPS in young rats. We assessed the rat?s motor performance and analyzed the cell number, morphology and reactivity of glial cells.Results: ICV IGF-1 treatment recovered motor impairment in both animal models. Regarding the aging model, we observed a significant increase in the microglial cells number in IGF-1 treated rats, accompanied by a significant increment in their reactivity, presenting a higher percentage of M2 phenotype number. With respect to astrocytes, though we did not observed a significant difference in the cell number, experimental rats showed a more complex phenotype.