scholarly journals Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson’s disease

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3099-3115 ◽  
Author(s):  
Mingli Li ◽  
Huadong Xu ◽  
Guoqing Chen ◽  
Suhua Sun ◽  
Qinglong Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Early Onset ◽  
D2 Receptor ◽  
Motor Symptom ◽  
Dopaminergic Transmission ◽  
Brain Circuits ◽  
Underlying Mechanisms

Anxiety is a major early-onset non-motor symptom in Parkinson’s disease, but the underlying mechanisms remain largely unknown. By imaging brain circuits in an awake parkinsonian mouse model, Li, Xu et al. provide evidence that Parkinson’s disease-associated anxiety is caused by impaired postsynaptic D2 receptor-dependent dopaminergic transmission in prefrontal cortex.

scholarly journals The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 841 ◽  
Author(s):  
Simoneide S. Titze-de-Almeida ◽  
Cristina Soto-Sánchez ◽  
Eduardo Fernandez ◽  
James B. Koprich ◽  
Jonathan M. Brotchie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Targets ◽  
Fine Tuning ◽  
Dopaminergic Transmission ◽  
Complementary Sequences ◽  
Autonomic Dysfunctions ◽  
Specific Regulation ◽  
Underlying Mechanisms ◽  
Cell Transcriptome

MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3’-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson’s disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression –a neuroprotective agent–remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics.

Catalpol Exerts Neuroprotective Effect on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Mouse Model of Parkinson’s Disease and the Underlying Mechanisms

2021 ◽  
Vol 11 (8) ◽  
pp. 1506-1516
Author(s):  
Xueqian Li ◽  
Chengzhi Zhao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Performance Test ◽  
Behavioral Science ◽  
Neuroprotective Effect ◽  
Inflammatory Factors ◽  
Sod Activity ◽  
Novel Approach ◽  
Underlying Mechanisms

Our current study aimed to assess the preventive and therapeutic impacts of catalpol on Parkinson’s disease (PD) and its possible mechanism. In this study, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were employed to establish a PD model and then treated with catalpol followed by analysis of behavioral science by open field test, pole-climbing assay and rotarod performance test, ROS and SOD activity and expression of TH, DAT, VEGF and GAP43 by western blot or immunofluorescence. The results disclosed that catalpol can ameliorate the MPTP-triggered loss of dopamine (DA)-producing neurons, while it was able to enhance the expression of tyrosine hydroxylase (TH), accompanied by the activation of astrocytes and microglia. Catalpol treatment significantly retarded the oxidative stress induced by MPTP, along with elevated levels of VEGF and growth-associated protein 4 (GAP43). Additionally, catalpol treatment activated the MKK4/JNK/c-Jun signal pathway in PD mouse model, accompanied by reduced secretion of pro-inflammatory factors. Catalpol executed the anti-apoptotic and anti-oxidant impacts on MPTP-induced Parkinson’s model, suggesting that it might be a novel approach for treating PD in the future.

scholarly journals Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: In vivo imaging with [18F]fallypride

2010 ◽  
Vol 25 (16) ◽  
pp. 2777-2784 ◽  
Author(s):  
Marta G. Vučcković ◽  
Quanzheng Li ◽  
Beth Fisher ◽  
Angelo Nacca ◽  
Richard M. Leahy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
In Vivo Imaging ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2

scholarly journals Distinct patterns of speech disorder in early-onset and late-onset de-novo Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jan Rusz ◽  
Tereza Tykalová ◽  
Michal Novotný ◽  
Evžen Růžička ◽  
Petr Dušek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Standard Deviation ◽  
Early Onset ◽  
De Novo ◽  
Late Onset ◽  
Age At Onset ◽  
Distinct Pattern ◽  
Speech Disorder ◽  
Motor Symptom

AbstractSubstantial variability and severity of dysarthric patterns across Parkinson’s disease (PD) patients may reflect distinct phenotypic differences. We aimed to compare patterns of speech disorder in early-onset PD (EOPD) and late-onset PD (LOPD) in drug-naive patients at early stages of disease. Speech samples were acquired from a total of 96 participants, including two subgroups of 24 de-novo PD patients and two subgroups of 24 age- and sex-matched young and old healthy controls. The EOPD group included patients with age at onset below 51 (mean 42.6, standard deviation 6.1) years and LOPD group patients with age at onset above 69 (mean 73.9, standard deviation 3.0) years. Quantitative acoustic vocal assessment of 10 unique speech dimensions related to respiration, phonation, articulation, prosody, and speech timing was performed. Despite similar perceptual dysarthria severity in both PD subgroups, EOPD showed weaker inspirations (p = 0.03), while LOPD was characterized by decreased voice quality (p = 0.02) and imprecise consonant articulation (p = 0.03). In addition, age-independent occurrence of monopitch (p < 0.001), monoloudness (p = 0.008), and articulatory decay (p = 0.04) was observed in both PD subgroups. The worsening of consonant articulation was correlated with the severity of axial gait symptoms (r = 0.38, p = 0.008). Speech abnormalities in EOPD and LOPD share common features but also show phenotype-specific characteristics, likely reflecting the influence of aging on the process of neurodegeneration. The distinct pattern of imprecise consonant articulation can be interpreted as an axial motor symptom of PD.

scholarly journals Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yazead Buhidma ◽  
Katarina Rukavina ◽  
Kallol Ray Chaudhuri ◽  
Susan Duty
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Predictive Validity ◽  
Molecular Mechanisms ◽  
Face Validity ◽  
Motor Symptom ◽  
Preclinical Models ◽  
Underlying Mechanisms ◽  
6 Hydroxydopamine

AbstractPain is a commonly occurring non-motor symptom of Parkinson’s disease (PD). Treatment of pain in PD remains less than optimal and a better understanding of the underlying mechanisms would facilitate discovery of improved analgesics. Animal models of PD have already proven helpful for furthering the understanding and treatment of motor symptoms of PD, but could these models offer insight into pain in PD? This review addresses the current position regarding pain in preclinical models of PD, covering the face and predictive validity of existing models and their use so far in advancing understanding of the mechanisms contributing to pain in PD. While pain itself is not usually measured in animals, nociception in the form of thermal, mechanical or chemical nociceptive thresholds offers a useful readout, given reduced nociceptive thresholds are commonly seen in PD patients. Animal models of PD including the reserpine-treated rat and neurodegenerative models such as the MPTP-treated mouse and 6-hydroxydopamine (6-OHDA)-treated rat each exhibit reduced nociceptive thresholds, supporting face validity of these models. Furthermore, some interventions known clinically to relieve pain in PD, such as dopaminergic therapies and deep brain stimulation of the subthalamic nucleus, restore nociceptive thresholds in one or more models, supporting their predictive validity. Mechanistic insight gained already includes involvement of central and spinal dopamine and opioid systems. Moving forward, these preclinical models should advance understanding of the cellular and molecular mechanisms underlying pain in PD and provide test beds for examining the efficacy of novel analgesics to better treat this debilitating non-motor symptom.

„Early Onset Parkinson's Disease“: Korrelation zwischen Alter bei Krankheitsbeginn und Verlauf?

2005 ◽  
Vol 32 (S 1) ◽  
Author(s):  
A Janzen ◽  
B Winner ◽  
M Lange ◽  
Z Kohl ◽  
K Pfeifer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Early Onset Parkinson’S Disease
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