IGF 1 GENE THERAPY PROMOTES SYNAPTIC REMODELING BY MICROGLIA

FALOMIR LOCKHART E; PENNINI JERÓNIMO; HEREÑÚ C.B.; DOLCETTI FRANCO; AREVALO MA.; BELLINI MJ; HERRERA MACARENA; SPITTAU

Congreso; SAN 2020; 2020

Microgliaare the resident immune cells of the central nervous system ( These cells play important roles in healthy and diseased brain in order tomaintain homeostasis One of these roles is the maintenance of synapses Microglia promote synaptogenesis by secreting growth factors and regulatethe number of synapses during the process of synaptic pruning In the adult CNS, microglial ramifications interact with synaptic terminals and synapticclefts, dendritic spines and astrocytic processes During aging, microglia go through an age related degeneration characterized by reduced migratory andphagocytic capacity, low production of neurotrophic factors and are more insensitive to stimuli Consequently, these alterations lead to an impairedsurveillance of the surrounding environment, impaired synaptic regulation and, therefore, loss of brain homeostasis Thus, it is of great interest to designstrategies to keep the microglia working correctly In this regard, IGF 1 gene therapy has shown to be able to act on aged microglia, promoting theirproliferation and increasing their reactivity in the Striatum Falomir Lockhart et al, 20191Evaluate the effects of IGF 1 gene therapy on microglia activation state and their phagocytic activity2Evaluate the effects of IGF 1 gene therapy on gene expression in the Striatum3Evaluate the relation between microglial activity and motor performancewe observed that the treatment is capable ofpolarizing the striated microglia towards an anti inflammatory phenotype Figure1 while increasing their phagocytic activity, promoting synaptic remodelingFigure 2 Moreover, we demonstrated that IGF 1 gene therapy downregulates theexpression of genes related to neuroinflammation in the Striatum Figure 3Furthermore, IGF 1 treatment improved motor performance of aged rats Figure 5without affecting other behavior Figure 4Our results prompt us to state that IGF 1 gene therapy could be afeasible therapeutical approach to modulate microglia phenotypes andneuroinflammation, ameliorating age associated motor impairment