Investigating novel roles of astrocytic PKM2 in regulating the number of inhibitory synapses

Abstract

Glial cells play an important role for regulating brain homeostasis by forming and eliminating synapses during brain development. However, the underlying mechanisms required for synapse formation and elimination are not well understood. In particular, the proteins that regulate synapse formation and elimination remain unknown. Conversely, the role of PKM2 protein, which is highly expressed in astrocytes, is well known in cancer cells but has not been studied in the brain. In this study, we found that astrocytic PKM2-deficient mice did not change the morphology and viability of astrocytes in the hippocampus. Additionally, although the number of excitatory synapses was not changed, the number of inhibitory synapses was significantly reduced. We also found that astrocytic PKM2-deficient mice showed repetitive behavior, behavioral phenotype associated with autism spectrum disorder (ASD) mouse model. Taken together, these results indicate that PKM2 plays an important role in regulating the number of inhibitory synapses and appropriate brain development and behavior.