Basic Science and Pathogenesis.

Background: Agora (https://agora.adknowledgeportal.org) is an openly available web resource developed to enable a broad spectrum of Alzheimer's disease (AD) researchers access to target-based evidence generated within the translational research portfolio of the National Institute on Aging (NIA).

Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses.

Several mental illnesses, characterized by aberrant stress reactivity, often arise after early-life adversity (ELA). However, it is unclear how ELA affects stress-related brain circuit maturation, provoking these enduring vulnerabilities. We find that ELA increases functional excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, resulting from disrupted developmental synapse pruning by adjacent microglia.