Intranasal Ketamine Alleviates Depressive-like Behaviors in Chronic Unpredictable Mild Stress Rats in Association with Hypothalamic NADH:Ubiquinone Oxidoreductase Subunit A10.
European journal of pharmacology July 19, 2026 Yongning Lv, Zihe Yang, Linjie Li et al.
Intranasal ketamine given twice weekly for two weeks to rats exposed to chronic stress improved depressive-like behaviors, restored hypothalamic neuronal structure, increased synaptic density, and enhanced mitochondrial ultrastructure. RNA sequencing and molecular validation identified increased expression of Ndufa10, a gene encoding a mitochondrial complex I subunit, and its protein NDUFA10 in the hypothalamus. Blocking mitochondrial complex I with rotenone reduced these behavioral and molecular effects, suggesting that mitochondrial complex I activity contributes to ketamine's antidepressant-like actions. α-Synuclein protein changed in parallel without corresponding mRNA changes, indicating a post-transcriptional alteration.