Activated cell-cycle CDK4/CyclinD1-pRB-E2F1 signaling pathway is involved in the apoptosis of dorsal raphe nucleus in the rat model of PTSD.

Dysregulation of the dorsal raphe nucleus (DRN) has been revealed to contribute to cognitive and arousal impairments associated with post-traumatic stress disorder (PTSD) in an animal model. In our research an acute exposure to single prolonged stress (SPS) was used to establish PTSD rat model and the effects related to cell-cycle signaling pathway in DRN were examined. Apoptosis in DRN was detected by TUNEL staining, showing that DRN apoptosis number was sharply increased after SPS. SPS triggered cell-cycle CDK4/CyclinD1-pRB-E2F1 signal pathway. Treatment with CDK4 inhibitor Abemaciclib successfully attenuated the DRN apoptosis and rescued decreased spatial learning and memory abilities in SPS rats, indicating that activation of CDK4/CyclinD1-pRB-E2F1 pathway was involved in DRN apoptosis, which may be one of the pathogenesis for PTSD. • Single prolonged stress (SPS) can lead to dorsal raphe nucleus (DRN) apoptosis. • Cell-cycle CDK4/CyclinD1-pRB-E2F1 pathway can be activated after exposure to SPS. • Cell-cycle CDK4/CyclinD1-pRB-E2F1 pathway activation may be one of the mechanisms for DRN apoptosis. • CDK4/CyclinD1-pRB-E2F1 pathway inhibition by CDK4 inhibitor Abemaciclib partly blocked SPS-induced apoptosis of DRN and rescued decreased spatial learning and memory abilities in SPS rats. • DRN apoptosis induced by CDK4/CyclinD1-pRB-E2F1 pathway might be one ot the pathogenesis for PTSD. [ABSTRACT FROM AUTHOR]