KEY FACTORS ASSOCIATED WITH TREATMENT-RESISTANT DEPRESSION- RELATED COGNITIVE DECLINE IN DIFFERENT AGE

Abstract Background Cognitive dysfunction is strongly associate with late-life depression. Previous study further indicated that treatment-resistant depression (TRD) patients, which refers poor responses to adequate antidepressant treatment, have prominent cognitive impairment. Moreover, the depression patients with cognitive impairment could be a risk factor for dementia. Recent study revealed that increase of eIF4E phosphorylation have found highly associate with cognitive dysfunction and depressive symptom. The antidepressant effect of low-dose ketamine, which effective in treating TRD, is involved in regulate eIF4E. Previous study further indicated dramatic increase of eIF4E phosphorylation was observed in post-mortem of Alzheimer's disease patients. As mention above, eIF4E may be considered a potential target crossing the cognitive dysfunction and depressive symptom underlying aging. Aims & Objectives We hypothesized that eIF4E phosphorylation may involve in cognitive dysfunction and depression, especially TRD, following aging. In present study, we performed the TRD mice model which induced by traumatic stress in young- and mid-age mice. Method We applied the traumatic stress to induce the TRD mice model. The behavior tests were examined the depressive-like behaviors. The synaptic plasticity such as long-term potentiation (LTP) was examine by electrical physiology. The phosphorylation of eIF4E was examine by western blotting. Results The results indicated that depressive-like behavior was found after traumatic stress in both young- and mid-age mice. While, the cognitive impairment induced by traumatic stress was worse in mid-age mice. Moreover, the increased eIF4E phosphorylation was greater after traumatic stress in mid-aged mice. The depressive-like behavior was improved by eIF4E phosphorylation inhibition. Furthermore, the cognitive impairment only improved by inhibition of eIF4E phosphorylation. Discussion & Conclusion Present study demonstrated the relationship between cognitive dysfunction and depression, especially TRD population, following aging. Our finding further provided the evidences that eIF4E may a key factor which highly associate with cognitive dysfunction and depression following aging. To date, effective therapeutic strategy for cognitive dysfunction with TRD remain urgent. EIF4E may be considered a potential target for this issue.