A single low dose of S-ketamine reduces depression- and anxiety-like behaviors in a rat model of postpartum depression (PPD) created by reproductive hormone withdrawal. The treatment also preserves synaptic plasticity in the hippocampus, as shown by molecular, structural, and electrophysiological measures. The findings suggest that maintaining synaptic plasticity is a key mechanism for S-ketamine's antidepressant effects in this PPD model.
Prenatal exposure to ketamine or its analog 2-fluorodeschloroketamine disrupts mitochondrial energy production in developing brain cells, increasing the risk of neurological damage. Using human cerebral organoids and single-cell RNA sequencing of 83,436 cells, the study found that both substances altered gene networks controlling mitochondrial oxidative phosphorylation in cortical cells. Experiments in fetal mouse neurons confirmed that exposure increased mitochondrial fragmentation and oxidative stress while reducing ATP production capacity. These energy disruptions during rapid brain development can make offspring more vulnerable to neurological issues. The results provide direct evidence of neurodevelopmental toxicity from these substances and identify mitochondrial dysfunction as a probable primary molecular mechanism.