Ketamine reverses chronic corticosterone-induced behavioral deficits and hippocampal synaptic dysfunction by regulating eIF4E/BDNF signaling.
Neuropharmacology December 15, 2024 Canyu Yang, Tahir Ali, Axiang Li et al. 11 citations
In a mouse model of depression induced by corticosterone, ketamine reversed depression-like behaviors and restored disrupted synaptic signaling, including the TrkB/BDNF and eIF4E/MNK1/p-eIF2α/ubiquitin pathways. Blocking eIF4E/MNK1 signaling with eFT508 prevented ketamine's antidepressant effects, but these were restored by 7,8-DHF, a BDNF/TrkB agonist. 7,8-DHF also increased eIF4E phosphorylation and MNK1 expression and enhanced p-eIF2α levels. Ketamine appears to act through the eIF4E/BDNF signaling pathway in the hippocampus, offering new insights into its molecular mechanism.