机构：[1]Department of Urology Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China[2]Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.[3]Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.[4]Department of Pathology, The First People's Hospital of Foshan, Foshan, Guangdong, China.[5]Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.[6]Graduate School, Shantou University Medical College, Shantou, Guangdong, China.[7]Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.[8]Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, Guangzhou, Guangdong, China.[9]Shantou University Mental Health Center, Shantou University Medical College, Shantou, Guangdong, China[10]National Key Disciplines, Department of Forensic and Pathology, Shantou University Medical College, Shantou, Guangdong, China[11]Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong, China.[12]Cell Biology Department, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.[13]The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.[14]Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.[15]Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China.[16]Gene Editing Center, School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China.[17]Department of Emergency Medicine and Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.[18]Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA.[19]Institute of Precision Cancer Medicine and Pathology, School of Medicine, and Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China.
Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.
基金：
National Natural Science Foundation of China (grants 82072683, 81773087, 81071736,
81572876, and 30973508 to HZ), the Natural Science Foundation of Guangdong Province of China
(grants 2021A1515012522, 9151018004000000, and 2022A1515010925 to HZ; 2021A1515011028 and
2022A1515011739 to HD), the Science and Technology Planning Project of Guangdong Province of China
(2019A030317024 to HZ), Special Project on the Integration of Industry, Education and Research of Guangdong Province (2011A090100024 to HZ), and Flagship Specialty Construction Project – General Surgery
(funding no. 711003 to YP and HZ).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区医学：研究与实验
最新[2025]版：
大类|1 区医学
小类|1 区医学：研究与实验
第一作者：
第一作者机构：[1]Department of Urology Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China[2]Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.[3]Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
共同第一作者：
通讯作者：
通讯机构：[2]Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.[19]Institute of Precision Cancer Medicine and Pathology, School of Medicine, and Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China.
推荐引用方式(GB/T 7714)：
Yao Zhimeng,Dong Hongmei,Zhu Jianlin,et al.Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment[J].JCI insight.2023,8(14):doi:10.1172/jci.insight.166306.
APA：
Yao Zhimeng,Dong Hongmei,Zhu Jianlin,Du Liang,Luo Yichen...&Zhang Hao.(2023).Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.JCI insight,8,(14)
MLA：
Yao Zhimeng,et al."Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment".JCI insight 8..14(2023)
医学