TIAM1-mediated synaptic plasticity underlies comorbid depression–like and ketamine antidepressant–like actions in chronic pain
Journal of Clinical Investigation December 15, 2022 Q. Ru, Yungang Lu, Ali Bin Saifullah et al.
Tiam1, a protein that regulates the structure of synapses, drives hyperactivity in the anterior cingulate cortex (ACC) by reorganizing the actin cytoskeleton and stabilizing NMDA receptors. This maladaptive synaptic plasticity underlies depressive-like behaviors in mouse models of chronic pain. Low-dose ketamine, an NMDA receptor antagonist, produces sustained antidepressant-like effects by blocking Tiam1-mediated changes in ACC neurons. The findings identify Tiam1 as a key molecular factor linking chronic pain to depression and as a target for ketamine's long-lasting effects.