Microglial brain-derived neurotrophic factor (BDNF) supports the behavioral and synaptogenic effects of ketamine
bioRxiv Preprint Server May 5, 2025 Samuel C. Woodburn, Alexander Kuhn, David T. Dadodsky et al. preprint
Microglial BDNF is necessary for ketamine to increase synaptic density in the prefrontal cortex and produce antidepressant-like behavioral effects. Ketamine injection increased BDNF expression in microglia from the prefrontal cortex. Depleting BDNF specifically from microglia reduced levels of the NMDA receptor subunit GluN2B in prefrontal synapses and weakened antidepressant-like responses to ketamine, while also preventing the increase in dendritic spine density normally caused by ketamine. These results show that microglia, not just neurons, contribute to ketamine's effects on brain connections and mood, expanding the understanding of how immune cells in the brain participate in antidepressant responses.