Depression(Dep)is one of the most common concomitant symptoms of Parkinson's disease(PD),but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep.Currently,the management of symptoms from b...Depression(Dep)is one of the most common concomitant symptoms of Parkinson's disease(PD),but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep.Currently,the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task.In this study,we found impaired activation of extracellular signal-related kinase(ERK),reduced levels of transcription and translation,and decreased expression of brain-derived neurotrophic factor(BDNF)in the medial prefrontal cortex(mPFC)of PD-Dep rats.We demonstrated that the abnormal phosphorylation ofα-synuclein(pS129)induced tropomyosin-related kinase receptor type B(TrkB)retention at the neuronal cell membrane,leading to BDNF/TrkB signaling dysfunction.We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation.The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression.In addition,a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.展开更多
基金supported by the National Natural Science Foundation of China(81974200 and 82371270).
文摘Depression(Dep)is one of the most common concomitant symptoms of Parkinson's disease(PD),but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep.Currently,the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task.In this study,we found impaired activation of extracellular signal-related kinase(ERK),reduced levels of transcription and translation,and decreased expression of brain-derived neurotrophic factor(BDNF)in the medial prefrontal cortex(mPFC)of PD-Dep rats.We demonstrated that the abnormal phosphorylation ofα-synuclein(pS129)induced tropomyosin-related kinase receptor type B(TrkB)retention at the neuronal cell membrane,leading to BDNF/TrkB signaling dysfunction.We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation.The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression.In addition,a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
