ObjectiveTo study the effect of rotenone on rat substantia nigra dopamine (DA) in the nervous system and oxidative stress parameters (malondialdehyde and glutathione), the influence of rotenone on DA neurons toxic effect and its pathogenesis. MethodsThis study applied back subcutaneous injection of rotenone in rats [1.0 mg/(kg·d)], and used immunocytochemistry technique to detect changes in the expression of tyrosine kinase (TH) in 10 rats of the control group and 10 rats of the experimental group. Spectrophotometry was used to detect the change of oxidative stress parameters in rats (malondialdehyde and glutathione). ResultsDA neurons in rats had various degrees of damage. The TH immune response strength of rats in the substantia nigra and striatum decreased significantly. The number of immune response nigra TH positive neurons was significantly less in the experimental group than in the control group (P< 0.01). Spectrophotometer method was used to detect the midbrain nigra of glutathione, which was significantly less in the experimental group than in the control group (P<0.01). Malondialdehyde in the experimental group was significantly higher (P<0.01). ConclusionRotenone has obvious neurotoxicity, and can lead to the damage of DA neurons and obvious oxidative stress injury in rats, which provides an experimental basis for the pathogenesis of Parkinson's disease, and at the same time provides new targets for the treatment.
PTEN-induced putative kinase 1 (PINK1), a Parkinson's disease (PD)-related protein, has two isoforms, the mitochondria-localized full-length isoform PINK1FL and the cytoplasm-localized short isoform PINK1-cyto. Studies have suggested that PINK1FL can selectively accumulate at the surface of damaged mitochondria and cooperate with another Parkinson's Disease-related protein PARKIN to trigger the degradation of MIRO1, a mitochondria trafficking regulator. The functions of PINK1-cyto are, however, not yet clear. To investigate the functions of PINK1-cyto, we expressed different proteins in cultured HEK293 cells by transfecting it with different plasmids, and detected the protein levels by Western blot after expressing for 24 h. We found that in cultured HEK293 cells, PINK1-cyto could also cooperate with PARKIN degrade MIRO1 in the presence of CK2β, and the regulatory subunit of Casein Kinase Ⅱ. Interestingly, this function of CK2β was not dependent on CK2α, the catalytic subunit of Casein Kinase II. We also found that CK2β could promote the direct interaction between PINK1-cyto and MIRO1 by immunocoprecipitation analysis. This result suggested that in addition to CK2α, CK2β could also form a kinase complex with PINK1-cyto with important physiological functions.
The aim of this study is to determine the regulatory mechanism of PTEN-induced putative kinase protein 1 short isoform (PINK1S) in cytoplasm. By co-immunoprecipitation (Co-IP) assay, we identified that PINK1S interacted with the beta regulatory subunit of Casein Kinase 2 (CK2β), but not with the catalytic subunits CK2α1 and CK2α2. Furthermore, cells were transfected with PINK1S and CK2β, and then PINK1S was purified by immunoprecipitation. After detecting the phosphorylated proteins by Phos-tagTM Biotin, we found that CK2β overexpression increased auto-phosphorylation of PINK1S. Finally, we generated CK2β knockdown cell lines by RNA interference. Purified PINK1S from CK2β knockdown cells significantly reduced its auto-phosphorylation compared with control cells. These results suggested that CK2β functions as a regulatory subunit of PINK1S kinase complex promoted its activation by self-phosphorylation.
Excessive microglial activation and subsequent neuroinflammation lead to neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases such as Parkinson's disease. The objective of this study was to determine the involvement of chlorpyrifos (CPF) in the activation of microglia and production of inflammatory factors in response to CPF stimulation and the influence on the viability of dopaminergic (DA) neurons. We detected the change of BV-2 cells morphology and expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) mRNA and protein level upon CPF stimulation (0, 1, 3, 6, 12, 24 h) in BV-2 (mouse brain microglia) cells by reverse transcription polymerase chain reaction (RT-PCR) or Western blot. We randomly assigned BV-2 cells into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. We stimulated The BV-2 cells in the CPF group with CPF, and we stimulated the two control groups with DMSO or NS for 12 hours, respectively. We then collected the used culture media from the culture dishes and centrifuged it to remove the detached cells. Then, we used the supernatants as microglial conditioned media. We treated SH-SY5Y neurons with various groups of microglial conditioned media for 24 hours. We observed the effect of conditioned media collected from BV-2 cell on the viability of dopaminergic cell lines SH-SY5Y using MTT assay. We found that inflammatory factors iNOS, COX-2 mRNA and protein levels were up-regulated upon CPF stimulation. Conditioned media from BV-2 upon CPF stimulation is toxic to SH-SY5Y. It might be concluded that the exposure to CPF may induce dopaminergic neuronal damage by the activation of inflammatory response, and a mechanism may be involved in Parkinson's disease pathogenesis.
ObjectiveTo systematically review the effectiveness and safety of rasagiline for Parkinson's disease. MethodsDatabases including The Cochrane Library (Issue 3, 2013), Web of Science, MEDLINE (Ovid), PubMed, CBM, CNKI, WanFang Data and VIP were electronically searched from inception to March 2013 for randomized controlled trials (RCTs) on rasagiline for Parkinson's disease. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of included studies. Meta-analysis was performed using RevMan 5.1 software. ResultsIn total, 6 studies involving 2 865 patients were included. The results of meta-analyses indicated that, compared with placebo, rasagiline 2 mg/d and 1 mg/d was significantly effective (MD=-3.16, 95%CI-3.21 to-3.11, P < 0.000 01; MD=-3.01, 95%CI-3.06 to-2.96, P < 0.000 01). Rasagiline 1 mg/d was more effective than rasagiline 2 mg/d in the treatment of early PD (MD=-0.65, 95%CI-0.73 to-0.57, P < 0.000 01). There was no significant difference between rasagiline and placebo in the incidences of nausea, headache, and dizziness (nausea:OR=0.72, 95%CI 0.49 to 1.07, P=0.60; headache:OR=1.02, 95%CI 0.70 to 1.49, P=0.91; dizziness:OR=0.87, 95%CI 0.49 to 1.55, P=0.35). ConclusionRasagiline is effective for early Parkinson's disease, and the dosage 1 mg/d is better than 2 mg/d based on current limited evidence. Rasagiline has a good tolerance and safety. Due to the limited quantity of the included studies and the evidence with limited strength, further high-quality RCTs are needed to verify the aforementioned conclusion.
ObjectiveTo systematically review the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in the treatment of Parkinson's disease patients with depression. MethodsThe Cochrane Library (Issue 5, 2014), PubMed, EMbase, CNKI, VIP and WanFang Data databases were searched from inception to May 2014 for randomized controlled trials (RCTs) investigating the efficacy and safety of SSRIs for Parkinson's disease patients with depression. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2 software. ResultsA total of 12 RCTs were included. The results of meta-analysis showed that the efficacy of SSRIs was better than placebo (RR=2.18, 95%CI 1.60 to 2.97, P<0.000 01) and the dropouts rates of SSRIs were higher than placebo (OR=3.02, 95%CI 1.04 to 8.79, P=0.04). However, the incidence rate of adverse events between the SSRIs group and the placebo group was not statistically different. ConclusionCurrent evidence indicates that SSRIs are effective for the Parkinson's disease patients with depression. Because of the limitation of quantity and quality of included studies, large-scale multi-center RCTs are required to confirm these findings.
Finger tapping test is a common testing item for patients with Parkinson's disease (PD) in clinical neurology. It mainly evaluates the fine motor function of patient's hand in three aspects:amplitude, speed and regularity of the movement. This paper focused on the quantitative assessment of regularity of finger tapping movement for PD patients. The movement signals of thumb and index finger were recorded by using inertial sensor unit in the process of tapping test. Two nonlinear dynamic indexes, approximate entropy (ApEn) and sample entropy (SampEn), were calculated, and then the values were statistically analyzed. The experimental results indicated that both indexes had significant differences between patient group and control group. Moreover, the indexes had relatively high correlation with the scores of corresponding unified Parkinson's disease rating scale (UPDRS) item rated by clinical clinician, which illustrated that these two indexes could reflect the injury level of the repetitive finger movement. So, as a reliable method, it can be provided to the clinical evaluation of hand movement function for PD patients.
Parkinson's disease (PD) diagnosis based on speech data has been proved to be an effective way in recent years. There are still some problems on preprocessing samples, ensemble learning, and so on. The problems can further cause misleading of classifiers, unsatisfactory classification accuracy and stability. This paper proposed a new diagnosis algorithm of PD by combining multi-edit sample selection method and random forest. At the end of it, this paper presents a group of experiments carried out with the newest public datasets. Experimental results showed that this proposed algorithm realized the classification of the samples and the subjects of PD. Furthermore, it achieved average classification accuracy of 100% and obtained improvement of up to 29.44% compared to those provided by the subjects. This paper proposes a new speech diagnosis algorithm for PD based on instance selection; and the method algorithm has a higher and more stable classification accuracy, compared with the other algorithms.
Feature representation is the crucial factor for the magnetic resonance imaging (MRI) based computer-aided diagnosis (CAD) of Parkinson’s disease (PD). Deep polynomial network (DPN) is a novel supervised deep learning algorithm, which has excellent feature representation for small dataset. In this work, a stacked DPN (SDPN) based ensemble learning framework is proposed for diagnosis of PD, which can improve diagnostic accuracy for small dataset. In the proposed framework, SDPN was performed on each subset of extracted features from MRI images to generate new feature representation. The support vector machine (SVM) was then adopted to perform classification task on each subset. The ensemble learning algorithm was then performed on all the SVM classifiers to generate the final diagnosis for PD. The experimental results on the Parkinson’s Progression Markers Initiative dataset (PPMI) showed that the proposed algorithm achieved the classification accuracy, sensitivity and specificity of 90.15%, 85.48% and 93.27%, respectively, with the brain network features, and it also got the classification accuracy of 87.18%, sensitivity of 86.90% and specificity of 87.27% on the multi-view features extracted from different brain regions. Moreover, the proposed algorithm outperformed other algorithms on the MRI dataset from PPMI. It suggests that the proposed SDPN-based ensemble learning framework has the feasibility and effectiveness for the CAD of PD.
ObjectiveTo observe the changes of optic disc structure and retinal nerve fiber layer thickness (RNFL) in patients with different degrees of Parkinson's disease (PD).MethodsThirty eyes of 30 patients with primary PD and 20 eyes of 20 healthy subjects (control group) in Xuanwu Hospital of Capital Medical University from October 2016 to October 2017 were enrolled in this study. The patients were divided into mild to moderate PD group (15 eyes of 15 patients) and severe PD group (15 eyes of 15 patients). All the patients underwent OCT examination. The optic disc area, cup area, C/D area ratio, rim volume, disc volume, cup volume, rim area, C/D area, linear C/D, vertical C/D, the thickness of average RNFL, superior, inferior, temporal upper (TU), superior temporal (ST), superior nasal (SN), nasal upper (NU), nasal lower (NL), inferior nasal (IN), inferior temporal (IT), temporal lower (TL) quadrant RNFL thickness. Analysis of variance was performed for comparison among three groups. Minimum significant difference t test was performed for comparison between two groups.ResultsOptic disc structure parameters: there was no significant difference in the area of optic disc between the three groups (F=1.226, P＞0.05). The other optic disc parameters were significantly different in the three groups (F=5.221, 5.586, 6.302, 5.926, 5.319, 5.404, 5.861, 6.603; P＜0.05). The cup area, cup volume, C/D area, linear C/D, vertical C/D of the mild to moderate PD group and severe PD group were higher than that of the control group (P＜0.05). The cup area, cup volume, C/D area, linear C/D, vertical C/D of the severe PD group were higher than those of mild to moderate PD group (P＜0.05), the rim area, rim volume and disc volume of the severe PD group were smaller than that of mild to moderate PD group (P＜0.05). The thickness of RNFL: there was no significant difference between the three groups of ST, SN, NU and NL (F=3.586, 2.852, 2.961, 2.404; P＞0.05). The average thickness of RNFL, TU, IN, IT and TL in patients of the mild to moderate PD group and severe PD group were less than that in the control group (P＜0.05). The thickness of the average RNFL, TU, IN, IT and TL in patients of the severe PD group were less than that in the mild to moderate PD group (P＜0.05). With the increase of PD severity, the RNFL of TL and TU thinned most significantly.ConclusionsWith the increase of the severity of PD, the optic disc structure and RNFL thickness changes obviously, showing reduced optic disc area and volume, enlarged cup area and volume significantly enlarged C/D ratio. The average RNFL thickness of PD patients is significantly thinner than that of the controls, and it is the most obvious in the TU and TL quadrant.