Effects of tricholoma matsutake polysaccharides on 1-methy-4-pehnyl-pyridine ion-induced PC12 cell damage / 解剖学报

Obｊective To investigate the protective mechanism of tricholoma matsutake polysaccharides(TMP) against 1-methy-4-pehnyl-pyridine ion (MPP

Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease

Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients.

Effect and molecular mechanism of mammalian target of rapamycin complex 2 / Akt signaling pathway on 6-hydroxydopamine-treated SH-SY5Y cell model / 解剖学报

[Abstract] Objective To study whether the regulation of mammalian target of rapamycin complex 2(mTORC2) / Akt signaling pathway has a protective effect on SH-SY5Y cell line damaged by 6-hydroxydopamine (6-OHDA), and to clarify its molecular mechanism. Methods SH-SY5Y cells treated with retinoic acid (RA) were given 6-OHDA, mTORC2 signaling pathway inhibitor PP242 and agonist A-443654 respectively. The changes of cell number in each group were investigated by immunofluorescent staining; The total protein was extracted and the expression level and interaction of key proteins in mTORC2 signaling pathway were determined by Western blotting and co-immunoprecipitation (CoIP); The apoptosis rate of cells in each group was detected by flow cytometry. At the same time, the co-culture Parkinson’ s disease (PD) model was made using SH-SY5Y cell line and Bv-2 cell line; MTT colorimetric method was used to detect the cell viability of each group; ELISA was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cell culture supernatant. Results The number of tyrosine hydroxylase(TH) / proliferating cell nuclear antigen (PCNA) / hochest-, TH / 5-bronmo-2’ -deoxyuridine(BrdU) -labeled positive cells in 6-OHDA-lesioned PD cell model group was significantly lower than that in the normal group; The apoptosis rate was higher; The expression of Rictor, p-Akt and regulated in DNA damage and development 1(REDD1) was increased; There was an interaction between Rictor and p-Akt or REDD1; The cell viability was significantly reduced in the co-culture model; the content of TNF-α and IL-β increased in the cell culture supernatant. With further up-regulation of the abovementioned protein expressions, the cell survival, apoptosis and pro-inflammatory cytokine levels in A-443654 group were significantly ameliorated, while PP242 group showed the opposite changes. Conclusion A-443654 activates mTORC2 signaling pathway by p-Akt, which increases the expression of Rictor and REDD1 protein. These changes contribute to the amelioration in cell survival rate, apoptosis rate, and the proliferation and differentiation and decreasion of apoptosis rate of SH-SY5Y cells. These result improved 6-OHDA-induced cell damage and inhibited the release of pro-inflammatory cytokines.

Purinergic ligand-gated ion channel 7 receptor-mediated cognitive impairment in Parkinson’s disease rats / 解剖学报

[Abstract] Objective To explore the role of purinergic ligand-gated ion chennel 7 receptor(P2X7R) in cognitive dysfunction in Parkinson’s disease rats. Methods Ninty rats was divided into 5 groups with 6 rats in each group with 3 repeats. The rat model of PD was established by 6-hydroxydopamine (6-OHDA). PD rats were injected with P2X7R agonists 2,3-adenosine 5-triethylammonium triphosphate (BzATP) and antagonists Comassie brilliant blue G (CBBG). The learning and memory ability and pain response of rats in the water maze were measured, and the expression of P2X7 in hippocampus was detected by Real-time PCR and Western blotting. Results Compared with the normal rats, PD rats had slow learning speed and weak memory ability. CBBG improved the learning and memory ability of PD rats, while BzATP decreased the learning and memory ability of PD rats. The result of Real-time PCR showed that compared with the control group, the expression of P2X7R mRNA was the highest in hippocampal tissue, the expression of P2X7R in CBBG group was down-regulated, and that of P2X7R in BzATP group was up-regulated. Compared with the PD group, Western blotting of P2X7R showed that the expression of P2X7 protein increased significantly in BzATP group, while the expression of P2X7 protein was lower in CBBG group. Conclusion Cognitive impairment exists in PD rats. CBBG can improve the learning and memory function of PD rats, and BzATP can inhibit the learning and memory function of PD rats.

Roscovitine rescuing neuronal loss and neuroinflammation in brain regions associated with Parkinson’s disease mice / 解剖学报

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

GABA / 中国生物化学与分子生物学报

Activation and inflammation of microglial correlate with progressive neuronal apoptosis in neurodegenerative disorders such as Parkinson’ s disease (PD). γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, has recently been shown to play an inhibitory role in the immune system, but the mechanism is unclear. In this study, the results showed that LPS promoted the release of inflammatory factors in a dose-dependent manner compared with the control group (P<0. 01). Meanwhile, cell viability and cytotoxicity assays showed that the released inflammatory factors could induce the decline of SH-SY5Y cell viability. BV2 microglia cells were pretreated with GABA and Muscimol, a GABA

Protective effect of long non-coding RNA cytoskeleton regulatory RNA targeting microRNA-1246 on cell damage in Parkinson' s disease models / 解剖学报

Objective To story the effect of long non-coding RNA (IncRNA) cytoskeleton regulatory RNA (CYTOR) targeting microRNA (miR)-1246 on cell damage in Parkinson' s disease (PD) models. Methods SK-N-SH cells were exposed to 100 |xmol/L 1 -methyl-4-phenylpyridinium (MPP

Correlation analysis of mental resilience and quality of life in patients with Parkinson's disease / 中国实用护理杂志

Objective:To investigate the relationship between mental resilience and quality of life in patients with Parkinson ′s disease and provide basis for paying attention to the mental health of this group. Methods:A total of 190 in patients with Parkinson ′s disease (PD) were selected from April to July 2017 in the First Affiliated Hospital of Dalian Medical University. The general data questionnaire, Mental Resilience Scale and 39-Item Quality of Life (QOL) Questionnaires were used to investigate among the patients. Results:The mental resilience score of PD patients was 48.0 (29.8, 62.2) points and the quality of life score was 56.0 (27.8, 82.0) points. There was a significant negative correlation between mental resilience and quality of life score ( r value was -0.538, P<0.01). Multivariate linear regression analysis showed that with the increase of psychological elasticity score, the score of quality of life decreased ( b value was -0.002, P<0.001). Conclusions:The mental resilience and quality of life of PD patients are both at a low level, the improvement of mental resilience is beneficial to improve their quality of life.

Current advances in understanding neuroprotective effect of acteoside in neurodegenerative disease / 中国药理学通报

Acteoside is among the most widespread of thedisaccharide caffeoyl esters that are widely distributed in the plant kingdom with diverse biological activities. Recent studies have shown that acteoside has neuroprotective activity in neurodegenerative diseases. This review examines and extrapolates from the recent literature to build support for the use of acteoside in mitigating neuropathy in neurodegenerative disease, including Parkinson ' s disease (PD) and Alzheimer' s disease (AD). We summarize the main pharmacokinetic parameters of acteoside in animals after different administration routes. Meanwhile, we point out both problems and shortcomings, and highlight its future development trend.

Analysis of molecular mechanism of Bushen Huoxue granules in treating Parkinson's disease based on network pharmacology and molecular docking / 中国药理学通报

Aim To analyze the molecular mechanism of Bushen Huoxue granules in the treatment of Parkinson's disease by using network pharmacology as the main research method combined with molecular docking technology. Methods TCMSP was used to find the active ingredients of Bushen Huoxue granules, and ADME screening was performed. The obtained active ingredients and targets were combined with PD targets to obtain disease-drug co-action targets; STRING 11.0 was used to construct PPI protein interaction network for the obtained disease-drugs. The Metascape platform was used to analyze the enrichment of disease-drug target functions and pathways, and then Cytoscape 3.7. 1 was used to construct a network diagram of Bushen Huoxue granules-PD targets-action pathways; AUTODOCK and PYMOL software were used for molecular docking and visualization operations. Results The core active ingredients of Bushen Huoxue granules in treating PD were quercetin, luteolin, kaempferol, tanshinone, etc.; the main targets were PTGS2, PTGS1, SCN5A, ADRB2 and CHRM1, etc.; the main signaling pathways are PI3K/AKT, Toll, whose function was mainly to regulate cell apoptosis and neuroinflammatory response. Conclusion This study has initially revealed the mechanism of Bushen Huoxue granules in the multi-level and multi-step treatment of PD, laying a foundation for future animal experiments.

Malnutrition and Associated Motor and Non-motor Factors in People with Parkinson's Disease

Background: People with Parkinson’s disease (PwP) are at higher risk of developing malnutrition. Several factors have been suggested to be involved including motor symptoms, non-motor symptoms, and treatment-related complications. Objective: The objective of the study was to analyze the combined effect of motor, non-motor, and pharmacological factors in the risk of malnutrition in PwP. Methods: Eighty-seven consecutive PwP were included in the study. Clinical data and pharmacological treatment were collected. Nutritional status was assessed using the Mini-Nutritional Assessment (MNA) questionnaire. Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Non-motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale HAM-D, and Montreal Cognitive Assessment were applied. Results: Thirty (34.4%) PwP were at risk of malnutrition and seven had malnutrition (8%). Abnormal nutritional status was associated with lower education, higher MDS-UPDRS Parts I, II, and III and total scores, and higher scores in the NMSS domain of sleep disorders and fatigue. MDS-UPDRS motor score remained as a determinant of abnormal nutritional status, defined as MNA <23.5, with an odds ratio 1.1 (95% confidence interval 1.01-1.10, p = 0.02). Conclusion: The main factor associated with nutritional status was severity of the motor symptoms as assessed by the MDS-UPDRS Part III. Non-motor symptoms and treatment-related complications were not associated with malnutrition. (REV INVEST CLIN. 2020;72(5):293-9)

Acortamiento de telómeros en enfermedades neurodegenerativas: implicaciones terapéuticas / Telomere attrition in neurodegenerative disorders: therapeutic implications

Introducción: Varias enfermedades neurodegenerativas están asociadas a la ocurrencia de acortamiento de los telómeros, y los convierten en biomarcadores y dianas terapéuticas potenciales. Objetivo: Reflejar la relevancia del acortamiento de los telómeros para enfermedades neurodegenerativas, y destacar sus implicaciones Material y métodos: Se realizó una revisión bibliográfica durante los meses de septiembre de 2019 a enero de 2020. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias sólidas de asociación entre el acortamiento de los telómeros y las enfermedades de Alzheimer y Huntington, que sugieren un papel relevante de la biología de los telómeros en la fisiopatología de estas enfermedades. Las evidencias disponibles hasta el momento no permiten establecer la relevancia de la biología de los telómeros en la fisiopatología de la Enfermedad de Parkinson o de la esclerosis lateral amiotrófica. Se obtuvieron evidencias de la utilidad de terapias orientadas a la prevención del acortamiento de los telómeros para el tratamiento de enfermedades neurodegenerativas. Conclusiones: El acortamiento de los telómeros es de relevancia fisiopatológica y clínica para las enfermedades de Alzheimer y Huntington, mientras que existen evidencias insuficientes para establecer su importancia en la Enfermedad de Parkinson y la esclerosis lateral amiotrófica. El uso de estrategias para estimular la actividad de la telomerasa tiene potenciales aplicaciones terapéuticas en el contexto de enfermedades neurodegenerativas(AU)

Introduction: Several neurodegenerative disorders are associated with telomere attrition, turning telomeres into potential biomarkers and potential therapeutic targets. Objective: To assess the relevance of telomere attrition for neurodegenerative disorders, highlighting its therapeutic implications. Material and methods: A literature review was carried out from September 2019 to January 2020. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence for an association between telomere attrition and Alzheimer and Huntington diseases was obtained, suggesting a potential importance of telomere biology in the physiopathology of these diseases. Current evidence does not allow establishing the relevance of telomere attrition in the physiopathology of Parkinson´s disease or Amyotrophic Lateral Sclerosis. Evidence was obtained for the usefulness of therapies for the prevention of telomere attrition in the treatment of neurodegenerative disorders. Conclusions: Telomere attrition has physiopathological and clinical relevance in Alzheimer´s and Huntington´s diseases, though current evidence is not enough to establish its role in Parkinson's disease and Amyotrophic Lateral Sclerosis. Strategies that enhance telomerase activity have therapeutic potential in the context of neurodegenerative disorders(AU)

Detection of intestinal microbial changes in rotenone-induced Parkinson' s disease model mice / 解剖学报

[Abstract] Objective To investigate the changes of intestinal microbes in rotenone-induced Parkinson' s disease (PD) mice based on 16S rRNA gene sequencing. Methods Fourteen 8-week-old male C57BL/6J mice were randomly divided into two groups: 6 mice in the control group and 8 mice in the model group. The model mice were injected subcutaneously with rotenone (3 mg/kg) for 5 weeks, and the bod)' weight was measured once a week. After 5 weeks, behavioral tests were perfonned, including the rotating rod test and the open field test. The contents of the tract were used for intestinal microbial detection analysis. Results After 5 weeks of rotenone treatment, the weight of PD mice was significantly lower than that of the control mice(P 0. 05), but the microbial species showed significant differences. Among them, the PD mice showed a significant decrease in the intestinal Turicibacter (P < 0 . 0 1), a significant increase in norank f Lachnospiraceae (P < 0. 01), a significant decrease in norank_f Erysipelotrichaceae(P<0. 01), and a significant increase in Lachnoclostridium{ P<0. 0 1) . Conclusion Intestinal microbes in PD mice are disordered, and these intestinal flora ma)' be involved in the development of dyskinesia in PD mice.

Role of sirt3 in molecular mechanism of melatonin protecting dopaminergic neurons in Parkinson' s disease / 中国药理学通报

Aim To investigate the role of SIRT3 in the molecular mechanism of melatonin protecting do-paminergic neurons in Parkinson' s disease ( PD). Methods Forty-eight mice were randomly divided into control group, model group and treatment group. The mice in treatment group received intraperitoneal injection of melatonin (10 mg • kg"1) and MPTP (30 mg • kg ~1). The mice in model group only received intraperitoneal injection of MPTP (30 mg • kg~1 ) , and the mice in control group received the same a-mount of normal saline. Melatonin was administered continuously for 14 days. The expressions of TH and lba-1 in substantia nigra were analyzed by immunohis-tochemistry. The levels of oxidative stress ( ROS, MDA, SOD) and inflammatory factors (TNF-a, IL-lp) in the midbrain were measured by ELISA. SIRT3 mRNA level was analyzed by qRT-PCR, and protein expression level was detected by immunocytochemistry assay and Western blot. Results Compared to control group, the TH expression decreased and Iba-1 expression increased in the substantia nigra, the oxidative stress and inflammatory injury in the midbrain were significantly enhanced, the SIRT3 mRNA and protein levels in the substantia nigra obviously declined, the SOD2 protein expression was also dramatically reduced, and the iNOS protein expression was elevated in model group; the differences between the groups were all statistically significant ( P < 0. 05 ). After treatment with melatonin, the TH expression increased, Iba-1 expression decreased, oxidative stress and inflammatory injury markedly decreased, SIRT3 mRNA and protein levels were elevated, SOD2 protein expression was up-regulated, and iNOS protein expression was down-regulated in treatment group. Compared to model group, the differences were all statistically significant ( P < 0.05). Conclusions Melatonin can counteract the damage of dopaminergic neurons by up-regulating the expression of SIRT3 in PD animal model. Its mechanisms of action are related to inhibiting microglia activation, and alleviating oxidative stress and inflammation injury.

Toxina botulínica para tratamento da sialorreia nos pacientes com doença de Parkinson / Botulinum toxin for treatment of sialorrhea in patients with Parkinson's disease

A sialorreia/ptialismo é um sintoma não motor frequente da doença de Parkinson, que pode causar impacto na saúde e na qualidade de vida dos pacientes. O sintoma decorre da combinação da disfagia com disautonomia e, muitas vezes, também do efeito adverso de drogas frequentemente utilizadas no tratamento de sintomas da doença, como por exemplo, os antipsicóticos atípicos e os inibidores da acetilcolinesterase. Diversas opções terapêuticas são utilizadas na prática clínica para controle da sialorreia, dentre elas, drogas anticolinérgicas ou antagonistas dos receptores adrenérgicos, injeção de toxina botulínica, cirurgia, radioterapia e terapias comportamentais e fonoaudiológicas. Este trabalho faz uma revisão das propostas terapêuticas até o presente momento para controlar a secreção de saliva dos pacientes com doença de Parkinson. A injeção de toxina botulínica nas glândulas salivares guiada por ultrassom é a opção com mais evidência de eficácia e segurança, de acordo com os últimos estudos.

Sialorrhea is a frequent nonmotor symptom in Parkinson´s disease (PD) that influences the patients' health and quality of life. The symptom arises from a combination of difficulty in swallowing saliva, autonomic dysfunction or as a side effect of frequent used drugs to control symptoms of the disease, as for example, atypical antipsychotics and acetylcholinesterase inhibitors. In clinical practice, different therapeutic approaches are used to control sialorrhea, such as anticholinergic or beta adrenergic antagonistic drugs, botulinum toxin injection, surgery, radiotherapy, behavioral psychotherapy and speech therapy. This paper reviews the therapeutic options available until now to control the loss of saliva from PD patient. Botulinum toxin injection in the salivary glands guided by ultrasound shows the best efficacy and security profile, according to the last published data.

Ritmo samba como estimulação auditiva rítmica e desempenho da marcha na doença de Parkinson / Samba rhythm for rhy thmic hearing stimulation and gait performance in Parkinson´s disease

A estimulação auditiva rítmica tem sido utilizada para amenizar as disfunções motoras na doença de Parkinson, no entanto não são evidentes as alterações que a música popular brasileira causa nos parâmetros espaço-temporais e desempenho funcional da marcha. O objetivo do estudo foi analisar o gênero musical samba durante a marcha de pacientes com doença de Parkinson em situações de dupla tarefa. Estudo de caráter transversal, descritivo e exploratório; cinco indivíduos atenderam aos critérios propostos e realizaram o Timed Up and Go Test nas situações sem música e música popular brasileira (samba) sensibilizadas com tarefas cognitivas e motoras para análise da marcha. Análise estatística descritiva e inferencial com teste de Fridman e post-hoc de Wilcoxon pareado (nível de significância de 5%). Evidenciou-se que o samba associado a uma tarefa motora reduziu a velocidade (p=0,01) e o comprimento de passos (p=0,04) quando comparados à condição de teste sem música. Ouvir música proporcionou maiores demandas atencionais, resultando na adoção de estratégias para diminuir as exigências de equilíbrio postural como a redução do comprimento do passo e velocidade e desta forma diminuir o risco de quedas em situações de duplas tarefas enquanto escuta música.

Rhythmic hearing stimuli have been employed to attenuate motor dysfunctions in Parkinson´s disease. However, changes that may be caused in space-time parameters and functional performance of gait brought about by Brazilian popular music are not always evident. Current analysis deals with the musical genre samba during gait of patients suffering from Parkinson´s disease in a twotask situation. Current transversal, descriptive and exploratory study comprised five agents who fulfilled criteria and undertook the Timed Up and Go Test in situations without music and with Brazilian popular music (samba) through cognitive and motor tasks for gait analysis. Descriptive and inferential statistical analysis with Friedman´s test and with paired Wilcoxon post-hoc test (at 5% significance) evidenced that samba associated with a motor task reduced the speed (p=0.01) and gait length (p=0.04) when compared to test conditions without any music. Listening to music demanded more attention and resulted in the use of strategies to decrease demands of posture balance, such as reduction in gait length and speed. Decrease in falling risks in a twotask situation while listening to music may occur.

Impacto da estimulação cerebral profunda na qualidade de vida e humor em pacientes com doença de Parkinson / Impact of deep brain stimulation on quality of life and mood in patients with Parkinson's disease

A doença de Parkinson (DP) é uma doença neurodegenerativa deri¬vada de uma redução da produção de dopamina. O seu tratamento é basicamente por medidas farmacológicas. No entanto, nos está¬dios avançados da doença, especialmente devido às flutuações do motor, o tratamento farmacológico por si só não é completamente bem-sucedido. Assim, surge a possibilidade de benefícios ao pacien¬te pela técnica de estimulação cerebral profunda (DBS). O objetivo deste estudo foi analisar o impacto do DBS palidal ou subtalâmica sobre a qualidade de vida desses pacientes (QoL). Para tanto, em¬pregaram-se duas escalas, comparando os resultados pré e pós-ope¬ratórios: o Inventário de Depressão de Beck - BDI (avalia o aspecto emocional dos pacientes) e o PDQ-39 (avalia os aspectos motores e as relações sociais). Podemos observar que a avaliação do BDI apon¬tou para uma melhora média de 9,5% e os escores do PDQ-39 me¬lhoraram 10,28%. Há evidências que pacientes submetidos à técnica de DBS subalâmicos ou paliativos mostraram uma QoL de melhoria importante, assim, o DBS surge como um adjuvante na luta contra a doença de Parkinson. (AU)

Parkinson's disease (PD) is a neurodegenerative disorder derived from a reduction of dopamine production. The treatment of PD is basically by pharmacological measures. However, in the advanced stages of the disease, especially due to motor fluctuations, phar¬macological treatment by itself is not completely successful. At that moment, the possibility of the patient´s benefits by the technique of deep brain stimulation (DBS) comes up. The aim of this study was to analyze the impact of pallidal or subthalamic DBS on PD patients' quality of life (QoL). To do so, two scales were employed, comparing the pre and post-operative results: Beck Depression Inventory - BDI (evaluates the patients' emotional aspect) and PDQ-39 (evaluates mo¬tor aspects and social relations). We could observe that BDI evalua¬tion pointed to an average improvement of 9.5% and PDQ-39 scores improved 10.28%. We can conclude that patients who have undergo¬ne the technique of subthalamic or pallidal DBS showed an important improvement QoL. DBS comes up as an adjuvant in the fight against Parkinson's disease. (AU)

The protective effects of cordycepin on MPTP-induced dopaminergic neuron damage in mice and its mechanism / 中国药理学通报

Aim To observe the protective effects of cordycepin ( Cor) on dopaminergic neurons in 1-meth-yl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine ( MPTP )-in-duced mouse model of Parkinson's disease ( PD) and to explore its mechanism. Methods C57BL/6 mice were administered with MPTP to establish the PD mod-el. Mice in Cor groups were pretreated with Cor (2.5,5.0 and 10.0 mg·kg-1 ) by intragastric administra-tion, respectively. The motor functions of the mice were observed in the open-field test, rotarod test and pole test. The content of DA, the numbers of TH-im-munoreactive cells and apoptotic cells were measured respectively by HPLC-ECD, immunohistochemistry staining and TUNEL staining. The expression of apop-tosis related proteins and MAPK signaling pathway-re-lated proteins ( p38 , p-p38 , ERK1/2 , p-ERK1/2 JNK1/2 and p-JNK1/2 ) were determined by Western blot. Results Cor could significantly improve the mo-tor dysfunction in PD mice. The contents of DA, DOPAC and HVA in the striatum remarkably increased after administration of Cor in MPTP-induced mice. Mo-reover, Cor could obviously reduce both the loss of TH-immunoreactive neurons and the numbers of TUNEL-positive cells in substantia nigra pars compacta ( SNpc) of PD mice. The protein expressions of Bax and cleaved caspase-3 were markedly down-regulated,whereas those of Bcl-2 and the ration of Bcl-2/Bax were significantly up-regulated by Cor pre-treatment followed by MPTP treatment. Furthermore, the protein expressions of p-p38 , p-ERK1/2 and p-JNK1/2 signif-icantly decreased in substantia nigra in Cor groups. Conclusions The results suggest that Cor can protect DA neurons against MPTP-induced injury by inhibiting apoptosis, which may be closely relevant to the inhibi-tion of MAPK signaling pathways.

Research progress on animal models of Parkinson's disease / 中国比较医学杂志

Parkinson's disease(PD)is a progressive neurodegenerative disorder, with an etiology that is now considered to be due to interaction between genetic and environmental factors. Typical PD features include loss of dopaminergic neurons in the nigrostriatal region, with typical motor traits of PD associated with dopamine deficiency. Animal models have contributed to determining PD etiology and pathogenesis,as well as testing new therapeutic schedules and novel drug research. Rodents, tree shrews, primates, and other animal models of PD have been established by different method. These models each have their own advantages and limitations, showing different clinical features and pathological mechanisms to those in humans. Therefore, the appropriate model for scientific research must be carefully considered. This article reviews the main neurotoxic and transgenic models of PD.