Objective: Impairment of basal ganglia (BG)‐thalamo‐cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.Methods: A total of 16 patients with tremor‐dominant (TD) PD, 23 patients with postural instability and gait difficulty‐dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel‐wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.Results: Compared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.Conclusions: The altered connectivity of BG‐cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.

Objectives: This study aimed to investigate the relationship between nutritional status and Parkinson's disease (PD) features.Methods: The cohort was composed of 556 Parkinson's patients who were admitted to the hospital. Patients were categorized as normal nutrition or at risk of malnutrition/already malnourished. Questionnaires, physical examinations, and biochemical tests were conducted. The relationship between nutrition status and PD was analyzed using t-tests, χ²-tests, and logistic regression models.Results: The prevalence of malnutrition [defined as a Mini Nutritional Assessment (MNA) score <17] was 39.2%, and 30.3% of patients were at risk of malnutrition (17 ≤ MNA score ≤ 23.5). There was no difference in gender and age between the different nutrition groups (P < 0.05). Patients at risk of malnutrition and those who were malnourished had a longer course of disease, more severe motor symptoms, a higher stage of PD according to the Hoehn and Yahr (H-Y) classification, a lower body mass index (BMI) index, a lower cognitive score, higher levels of depression and anxiety, and more serious non-motor symptoms (P < 0.05) than patients with normal nutrition. There were differences in adenosine deaminase, albumin, phosphorus, chlorine, total protein, and uric acid between the two groups (P < 0.05). High Unified PD Rating Scale (UPDRS-III) scores, high H-Y stages, and dyskinesia were risk factors for malnutrition in PD patients, while high levels of total protein, uric acid, and chlorine were protective factors that led to good nutrition (P < 0.05).Conclusions: Our results showed that dyskinesia, disease severity, total protein levels, uric acid levels, and chlorine levels were associated with nutritional status among Chinese PD patients. The findings of this study indicate the significance of the early detection and prevention of malnutrition to improve the quality of life of PD patients.

Hydrogen sulfide (H₂S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular system. However, the mechanism by which H₂S elicits neuroprotective effects in the progression of Parkinson’s disease (PD) remains unclear. To investigate the role of H₂S in delaying the pathological process of PD, we used the most common sodium hydrosulfide (NaHS) as an H₂S donor and established a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) in the present study. Our results show that H₂S reduced neuronal loss during the progression of PD. Notably, we found that H₂S exhibited protective effects on dopaminergic neurons. Excitingly, H₂S also increased the proliferation of neural stem cells in the subventricular zone. Next, we evaluated whether the neuroprotective effects of H₂S on dopaminergic neurons in PD are dependent on adult nerve regeneration by treating primary adult neural stem cells cultured ex vivo with 1-methyl-4-phenylpyridine. Our results show that H₂S could prevent nerve injury induced by 1-methyl-4-phenylpyridine, promote the growth of neurospheres, and promote neurogenesis by regulating Akt/glycogen synthase kinase-3β/β-catenin pathways in adult neural stem cells. These findings confirm that H₂S can increase neurogenesis in an adult mouse model of PD by regulating the Akt/glycogen synthase kinase-3β/β-catenin signaling pathway. This study was approved by the Animal Care and Use Committee of Nanjing Medical University, China (IACUC Approval No. 1601153-3).

Aims: SUMOylation is a posttranslational modification related to multiple human diseases. SUMOylation can be reversed by classes of proteases known as the sentrin/SUMO‐specific proteases (SENPs). In the present study, we investigate the potential role of SENP1 in pericytes in the brain ischemia.Methods: Pericyte‐specific deletion of senp1 mice (Cspg4‐Cre; senp1^f/f) were used for brain function and neuronal damage evaluation following brain ischemia. The cerebral blood vessels of diameter, velocity, and flux were performed in living mice by two‐photon laser scanning microscopy (TPLSM). Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of pericyte‐specific SENP1 in the pathological process of brain ischemia. A coculture model of HBVPs and HBMECs mimicked the BBB in vitro and was used to evaluate BBB integrity after glucose deprivation.Results: Our results showed that senp1‐specific deletion in pericytes did not affect the motor function and cognitive function of mice. However, the pericyte‐specific deletion of senp1 aggravated the infarct size and motor deficit following focal brain ischemia. Consistently, the TPLSM data demonstrated that SENP1 deletion in pericytes accelerated thrombosis formation in brain microvessels. We also found that pericyte‐specific deletion of senp1 exaggerated the neuronal damage significantly following brain ischemia in mice. Moreover, SENP1 knockdown in pericytes could activate the apoptosis signaling and disrupt the barrier integrity in vitro coculture model.Conclusions: Our findings revealed that targeting SENP1 in pericytes may represent a novel therapeutic strategy for neurovascular protection in stroke.

Objective: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China.Methods: The cross‐sectional community‐based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition.Results: Among the 2,663 dementia‐free and Parkinson disease (PD)‐free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS‐III score (r = −0.456, p = 0.004).Conclusion: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.

The aim of the present study was to screen for biomarkers of Parkinson's disease (PD) using proteomics and bioinformatics approaches. PD patients were divided into three groups: Those without surgery (PD1 group); those who had undergone deep brain stimulation (DBS) surgery without electrode stimulation (PD2 group); and those who had undergone DBS surgery with 1 month of electrode stimulation (PD3 group). The non‑Parkinson control group (CK group) was also involved. Quantitative proteomic analysis of human sera was performed through the use of tandem mass tag markers and liquid chromatography‑mass spectrometry (LC‑MS)‑based techniques. For the proteins with quantitative information, a systematic bioinformatics analysis was then performed, including protein annotation, functional classification, functional enrichment and cluster analysis based on functional enrichment. Of the 739 proteins identified, quantitative information was available for 644. With regard to differential expression, 18 upregulated and 21 downregulated proteins were screened in the PD1/CK comparison group; 12 upregulated and 12 downregulated proteins in the PD2/PD1 comparison group; and 16 upregulated and 19 downregulated proteins in the PD3/PD2 comparison group. Coiled‑coil domain‑containing protein 154 (CCDC154) and tripartite motif‑containing protein 3 (TRIM3) were key proteins involved in the molecular mechanisms of PD, participating in intracellular vesicle, ubiquitin protein ligase and transition metal ion‑binding activities. After DBS surgery, desert hedgehog protein (DHH) was downregulated, whereas neuropilin‑2 (NRP2) was upregulated; these participated in the ensheathment of neurons and the semaphorin receptor complex, respectively. The expression level of chloride intracellular channel protein 1 (CLIC1) was increased after 1 month of electrode stimulation following DBS. By combining proteomic approaches and LC‑MS methods, significant proteins including CCDC154, TRIM3, DHH, NRP2 and CLIC1 were detected with high specificity and sensitivity. These may be used as novel biomarkers for early diagnosis of PD and the future development of treatments.