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World Journal of Gastroenterology 2006年第31期12卷 4966-4972页

作者： Deng-Fu Yao Wei Wu Min Yao Li-Wei Qiu Xin-Hua Wu Xiao-Qin Su Li Zou Deng-Bing Yao Xian-Yong Meng Research center of Clinical Molecular Biology Affiliated Hospital Nantong University Nantong 226001 Jiangsu Province China Nanjing University Nanjing 210008 Jiangsu Province China center of Oncology Affiliated Hospital of Nantong University Nantong 226001 Jiangsu Province China Institute of Neurosciences Nantong University Nantong 226001 Jiangsu Province China Department of Gastroenterology Affiliated Hospital Nantong University Nantong 226001 Jiangsu Province China

瞄准：在肝纸巾或外部血在肝细胞癌(HCC ) 和它的诊断含意的开发期间调查 telomerase 表示的动态改变为 HCC 的单音的原子房间。方法：肝 telomerase 的动态表情在 hepatocytes 的恶意的转变期间被观察在(SD ) Sprague-Dawly，老鼠用 0.... 详细信息

瞄准：在肝纸巾或外部血在肝细胞癌(HCC ) 和它的诊断含意的开发期间调查 telomerase 表示的动态改变为 HCC 的单音的原子房间。方法：肝 telomerase 的动态表情在 hepatocytes 的恶意的转变期间被观察在(SD ) Sprague-Dawly，老鼠用 0.05% 2-fluoenyacetamide (2-FAA ) 喂了。全部的 RNA 和 telomerase 从老鼠或人的肝纸巾被提取。在肝并且在传播的血的 telomerase 活动被 telomeric 重复扩大 protocol-enzyme-linked 免疫吸着剂试金(TRAP-ELISA ) 检测，并且它的诊断价值与良性或恶意的肝疾病在病人被调查。结果：肝细胞瘤模型在 HCC 开发期间显示了肝的 telomerase 的动态表示。telomerase 活动与肝总数 RNA 层次一致(r = 0.83， P<0.01 ) 在 hepatocytes 的退化，初癌状态，和癌化的阶段。在 HCC 病人，在 HCC 纸巾的 telomerase 层次比在他们的邻近的非癌的纸巾，而是肝全部的 RNA 铺平显著地高比在后者在前者是更低的。尽管 HCC 病人的传播 telomerase 反常地与长期的肝疾病在病人之中被表示，因为发生在正常控制是15.7%， telomerase 活动是为 HCC 诊断的一个非特定的标记，25%在长期的肝炎，45.9%在肝肝硬化，并且85.2%在 HCC ，分别地吸收度什么时候 telomerase 活动珍视，是超过 0.2 。如果价值是超过 0.6，发生在 HCC 组是 60% 并且 0% 在除了在有肝的二种情况中的其它(P<0.01 ) 的任何东西肝硬化。然而，有浆液 alpha-fetoprotein 水平的传播 telomerase 的联合能增加积极的率和精确性(92.6% ， 135 中的 125 个) HCC 诊断。结论：过去 telomerase 的表示在肝纸巾与 HCC 开发，和它的反常被联系或在外设，血能是为 HCC 的诊断和预后的一个有用标记。

关键词：动力学酶活性诊断方法肝疾病肝细胞癌

Identification of key genes involved in axon regeneration and Wallerian degeneration by weighted gene co-expression network analysis

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Neural Regeneration Research 2022年第4期17卷 911-919页

作者： Yan Lu Qi Shan Mei Ling Xi-An Ni Su-Su Mao Bin Yu Qian-Qian Cao Key Laboratory of Neuroregeneration of jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina School of Life Sciences Nantong UniversityNantongJiangsu ProvinceChina

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.

关键词： axon regeneration extracellular signal-regulated kinase signaling pathway hub genes Kif22 peripheral nerve injury protein kinase Cα Schwann cells Wallerian degeneration weighted gene co-expression network analysis

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 893-906页

作者： Yao Zhou Xiao-Lei Zhang Hong-Xia Ni Tian-Jing Shao Ping Wang Department of Operating Room Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina Department of Gastrointestinal Surgery The Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older people.Surgical management,despite advancements,requires careful consideration of preoperative patient status for optimal outcomes.AIM To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery.METHODS A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis.Only studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were included.Pooled effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were included.Compared with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow up.Frail patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control group.The risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail patients.CONCLUSION Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased mortality.Integrating frailty assessment appears crucial for tailored surgical management.

关键词： Frailty Frail adults Colorectal surgery Colorectal cancer Complications Mortality Survival Slinical outcomes Meta-analysis

Transcriptional regulatory network during axonal regeneration of dorsal root ganglion neurons:laser-capture microdissection and deep sequencing

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Neural Regeneration Research 2023年第9期18卷 2056-2066页

作者： Li-Li Zhao Tao Zhang Wei-Xiao Huang Ting-Ting Guo Xiao-Song Gu Model Animal Research center and MOE Key Laboratory of Animal Models of Disease Nanjing UniversityNanjingJiangsu ProvinceChina Key Laboratory of Neuroregeneration of jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina School of Medicine and Life Sciences Nanjing University of Chinese MedicineNanjingJiangsu ProvinceChina

The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.

关键词： Arid5a Atf3 Crem dorsal root ganglion Fosl1 Klf6 laser-capture microdissection neuron smart-seq2 gene expression profile transcription factor

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

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中国神经再生研究：英文版 2023年第8期18卷 1847-1851页

作者： Yu-Mei Feng Jian Shao Min Cai Yi-Yue Zhou Yi Yao Jia-Xi Qian Zi-Han Ding Mao-Rong Jiang Deng-Bing Yao School of Life Sciences Key Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCoinnovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina Nantong University Xinglin College NantongJiangsu ProvinceChina

Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.

关键词： adeno-associated virus dorsal root ganglion lncRNA H19 nerve degeneration nerve regeneration peripheral nerve rat sciatic nerve injury semaphorin 6D Wallerian degeneration

Role of glycolysis in diabetic atherosclerosis

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World Journal of Diabetes 2023年第10期14卷 1478-1492页

作者： Qian-Jia Liu Wei Yuan Ping Yang Chen Shao Department of Cardiology Affiliated Hospital of Jiangsu UniversityZhenjiang 212000Jiangsu ProvinceChina

Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels.Atherosclerosis(AS)is one of the most common complications of diabetes.Modern lifestyles and trends that promote overconsumption and unhealthy practices have contributed to an increase in the annual incidence of diabetic AS worldwide,which has created a heavy burden on society.Several studies have shown the significant effects of glycolysis-related changes on the occurrence and development of diabetic AS,which may serve as novel therapeutic targets for diabetic AS in the future.Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall.In particular,it plays a vital role in the physiological and pathological activities of the three important cells,Endothelial cells,macrophages and vascular smooth muscle cells.There are lots of similar mechanisms underlying diabetic and common AS,the former is more complex.In this article,we describe the role and mechanism underlying glycolysis in diabetic AS,as well as the therapeutic targets,such as trained immunity,microRNAs,gut microbiota,and associated drugs,with the aim to provide some new perspectives and potentially feasible programs for the treatment of diabetic AS in the foreseeable future.

关键词： Atherosclerotic plaque Hyperglycemia Trained immunity microRNAs Gut microbiota Drugs

Transcriptomic analysis reveals essential microRNAs after peripheral nerve injury

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Neural Regeneration Research 2021年第9期16卷 1865-1870页

作者： Yu Wang Shu Wang Jiang-Hong He Key Laboratory for Neuroregeneration of jiangsu province and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina

Studies have shown that microRNAs(miRNAs) mediate posttranscriptional regulation of target genes and participate in various physiological and pathological processes, including peripheral nerve injury. However, it is hard to select key miRNAs with essential biological functions among a large number of differentially expressed miRNAs. Previously, we collected injured sciatic nerve stumps at multiple time points after nerve crush injury, examined gene changes at different stages(acute, sub-acute, and post-acute), and obtained mRNA expression profiles. Here, we jointly analyzed mRNAs and miRNAs, and investigated upstream miRNAs of differentially expressed mRNAs using Ingenuity Pathway Analysis bioinformatic software. A total of 31, 42, 30, and 23 upstream miRNAs were identified at 1, 4, 7, and 14 days after rat sciatic nerve injury, respectively. Temporal expression patterns and biological involvement of commonly involved upstream miRNAs(miR-21, let-7, miR-223, miR-10 b, miR-132, miR-15 b, miR-127, miR-29 a, miR-29 b, and miR-9) were then determined at multiple time points. Expression levels of miR-21, miR-132, miR-29 a, and miR-29 b were robustly increased after sciatic nerve injury. Biological processes involving these miRNAs include multicellular organismal response to stress, positive regulation of the epidermal growth factor receptor signaling pathway, negative regulation of epithelial cell differentiation, and regulation of myocardial tissue growth. Moreover, we constructed mechanistic networks of let-7, miR-21, and miR-223, the most significantly involved upstream miRNAs. Our findings reveal that multiple upstream miRNAs(i.e., let-7, miR-21, and miR-223) were associated with gene expression changes in rat sciatic nerve stumps after nerve injury, and these miRNAs play an important role in peripheral nerve regeneration. This study was approved by the Experimental Animal Ethics Committee of jiangsu province of China(approval No. 20190303-18) on March 3, 2019.

关键词： bioinformatic analysis Ingenuity Pathway Analysis mechanistic network microRNA peripheral nerve injury peripheral nerve regeneration RNA sequencing sciatic nerve crush

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke

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Neural Regeneration Research 2023年第5期18卷 1033-1039页

作者： Xiao-Wei Cao Hui Yang Xiao-Mei Liu Shi-Ying Lou Li-Ping Kong Liang-Qun Rong Jun-Jun Shan Yun Xu Qing-Xiu Zhang Department of Neurology of Drum Tower Hospital Medical School and the State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingJiangsu ProvinceChina Nanjing Drum Tower Clinical College of Xuzhou Medical University NanjingJiangsu ProvinceChina Institute of Brain Sciences Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu province Stroke center for Diagnosis and Therapy NanjingJiangsu ProvinceChina Nanjing Neurology Clinic Medical center NanjingJiangsu ProvinceChina Department of Neurology Lianyungang Municipal HospitalAffiliated Hospital of Xuzhou Medical UniversityLianyungangJiangsu ProvinceChina Department of Neurosurgery of Drum Tower Hospital Medical School and the State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingJiangsu ProvinceChina Department of Neurosurgery Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and Immunology and Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Second Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.

关键词： a disintegrin and metalloprotease domain 17 cerebral ischemia/reperfusion C-X3-C motif chemokine ligand 1 GW280264x microglia neuroinflammation postsynaptic density-93 Tat-CX3CL1(357–395aa)

Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury

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Neural Regeneration Research 2023年第6期18卷 1339-1346页

作者： Chen Chen Huiyuan Ji Nan Jiang Yingjie Wang Yue Zhou Zhenjie Zhu Yuming Hu Yongjun Wang Aihong Li Aisong Guo Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine The Second Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Traditional Chinese Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.

关键词： 25-hydroxycholesterol astrocyte chemotaxis cholesterol metabolism cholesterol-25-hydroxylase lipid homeostasis macrophage PAR1 spinal cord injury thrombin

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson’s disease

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Neural Regeneration Research 2023年第5期18卷 1107-1117页

作者： Chuan-Xi Tang Jing Chen Kai-Quan Shao Ye-Hao Liu Xiao-Yu Zhou Cheng-Cheng Ma Meng-Ting Liu Ming-Yu Shi Piniel Alphayo Kambey Wei Wang Abiola Abdulrahman Ayanlaja Yi-Fang Liu Wei Xu Gang Chen Jiao Wu Xue Li Dian-Shuai Gao Department of Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Experinental Teaching center of Morphology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Affiliated Suqian Hospital of Xuzhou Medical UniversitySuqianJiangsu ProvinceChina Department of Rehabilitation Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Medicine Jiangnan UniversityWuxiJiangsu ProvinceChina Department of Nursing Care the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.

关键词： cognitive impairment degree centrality dendritic spine dopamine transmission dopamine transporter glial cell line-derived neurotrophic factor Parkinson’s disease prefrontal cortex synaptic plasticity