IGF1 gene therapy promotes synaptic remodeling by microglia

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

virtual

Congreso; The Virtual Congress on Brain Health, Innovation & Technologies; 2020

Bioevents Ltd.

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 cells promote synaptogenesis by secreting growth factors and regulate the number of synapses during the process of synaptic pruning. In the adult CNS, the ramifications of the microglia interact directly 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 and studied how it affected microglial activity on female aged rats of 28 months-old. We observed that, after the treatment, microglia presented 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.