IGF-1 gene therapy modulates glial cell in neurodegenerative process.

HEREÑÚ C.B; HERRERA M.; CHAMPARINI LEANDRO; FALOMIR LOCKHART E; DOLCETTI FRANCO; PENNINI JERÓNIMO; BELLINI MJ

virtual 2020

Congreso; SAIC 2020; 2020

REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020

The natural process of aging and Parkinson´s disease (PD) are both neurodegenerative disorders with glial changes and progressive neuronal loss with a variety of motor and non-motor dysfunctions. It has been reported that the progression of many neurodegenerative diseases depends on the activation of microglia and their polarization towards a proinflammatory phenotype and establish an exacerbated immune response. Many neurotrophic factors produced by glial cells, such as Insulin like growth factor 1 (IGF1), can modulate glial cells phenotype, promoting neuronal survival. IGF-1 could be neuroprotective in neurodegenerative models by improving changes in neuronal and glial activity. Our research group has set the goal to fight the deleterious effects of aging in senile rats and 6OH Dopamine animal model to understand plasticity processes associated with behavior decline, analyze modifications on glial cells through different brain areas involved in the proposed circuit and to carry out therapeutic approaches with IGF-1 gene therapy. We showed that IGF1 gene therapy in senile rats increased the number of microglial cells, specifically in the Striatum. In addition, these cells presented higher reactivity and were polarized towards an M2 anti-inflammatory phenotype and those treated with RAd-IGF1 presented higher phagocytic activity and greater synaptic remodeling. Moreover, in PD animal model, we found an early behavioral cognitive decline that was partially modified with IGF1 overexpression on ongoing experiments. We observed astrocytes changes in different dorsal hippocampus areas and changes of TH reactivity that correlates with IGF-I overexpression. Conclusion: Further understanding of glial cells and their functions could allow modulation of the microenvironment resulting in potential therapeutic strategies, such as IGF-1 gene therapy, that improve the course and progression of the neurodegenerative process.