IGF1 gene therapy promotes synaptic remodeling by microglia

MACARENA LORENA HERRERA; BJÖRN SPITTAU; EUGENIA FALOMIR-LOCKHART; JERONIMO PENINNI; CLAUDIA B HEREÑÚ; FRANCO JUAN CRUZ DOLCETTI; ANGELES AREVALO; MARIA JOSÉ BELLINI

Simposio; 3rd Symposium on Physiology and pathology of neuroglia. Modalidad Virtual.; 2020

Microglia are the resident immune cells of the central nervous system (CNS). These cells play important roles in healthy and diseased brain in order to maintain homeostasis. One of these roles is the maintenance of synapses. Microglia promote synaptogenesis by secreting growth factors and regulate the number of synapses during the process of synaptic pruning. In the adult CNS, microglial ramifications interact with synaptic terminals and synaptic clefts, dendritic spines and astrocytic processes. During aging, microglia go through an age-related degeneration characterized by reduced migratory and phagocytic capacity, low production of neurotrophic factors and are more insensitive to stimuli. Consequently, these alterations lead to an impaired surveillance of the surrounding environment, impaired synaptic regulation and, therefore, loss of brain homeostasis. Thus, it is of great interest to design strategies to keep the microglia working correctly. In this regard, IGF1 has shown to be able to act on aged microglia, promoting their proliferation and their phagocytic capacity. We implemented IGF1 gene therapy in aged rats of 28 months-old and studied how it affected microglial activity. We observed that microglia increased phagocytic activity and synaptic remodeling. Moreover, these animals presented better motor performance. These results suggest that IGF1 gene therapy could be an effective treatment to modulate microglia activation and promote motor improvement.