Esketamine, a drug approved for treatment-resistant depression, may also treat postpartum depression (PPD) and reduce depression risk in offspring. In a mouse model of chronic unpredictable mild stress during pregnancy, both mothers with PPD and their adult offspring showed anxiety- and depression-like behaviors. Injecting esketamine into postpartum mice improved these behaviors: it enhanced exploration in unfamiliar environments, increased preference for sucrose, and restored impaired BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus. The findings suggest esketamine has potential for treating PPD and lowering the incidence of depression in the next generation.
Esketamine given to mice after traumatic brain injury (TBI) improved neurological outcomes, reduced neuronal death, and lessened neuroinflammation. The drug suppressed astrocyte activation, inhibited pro-inflammatory A1 astrocyte differentiation, and promoted protective A2 astrocyte formation. These effects occurred through inhibition of the METTL5/c-Myc/PD-L1 signaling pathway. The findings suggest esketamine has significant anti-inflammatory and neuroprotective properties that could be relevant for treating TBI.