Death-associated Protein Kinase 1 Impairs the Hippocampo-prefrontal Cortical Circuit and Mediates Post-stroke Depression

Xiao Ke, Sehui Ma, Yufen Zhang, Yao Yi, Hongyan Yu, Dian Yu, Lei Pei
2018 Exploratory Research and Hypothesis in Medicine  
Post-stroke depression (PSD) is a common and complex post-stroke neuropsychiatric disorder, which not only delays functional recovery but also increases mortality, and which currently lacks effective drug therapy. The pathogenesis of PSD is associated with impairment of the subcortical neural circuits and alterations of synaptic plasticity and neurotransmitters, but the exact mechanisms of PSD remain unknown. Our previous work indicates that the death-associated protein kinase 1 (DAPK1)
more » ... neuronal death after stroke. Genetic deletion of DAPK1 gene or blocking DAPK1 signal in the PSD mouse model can not only alleviate cerebral ischemic injury but also relieve PSD-like behaviors. Our previous work has also demonstrated the following results. First, the neural circuit of dorsal CA1 (dCA1) to medial prefrontal cortex (mPFC) (dCA1-mPFC) is selectively impaired after stroke. Second, the DAPK1 signal is involved in the impairment of dCA1-mPFC neural circuit after stroke. Third, genetic deletion of the DAPK1 gene or blocking of the DAPK1 signal alleviates the injury of dCA1-mPFC neural circuit after stroke and improves PSD-like behaviors. In conclusion, we hypothesize that activated DAPK1 signal after stroke induces apoptosis in the hippocampal dCA1 neurons, leading to loss of the dCA1-mPFC glutamatergic projections, synaptic injury, decrease of glutamate release, inhibition of mPFC neurons, and finally onset of PSD. We hope to further replenish the mechanisms of PSD and provide new insights for PSD treatment.
doi:10.14218/erhm.2018.00018 fatcat:wa3rrlej75eotgs4lflahgcnaa