scholarly journals Reduced Interaction of VAMP2 and Aggregated α-synuclein by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease.

2020 ◽  
Author(s):  
Kyungri Kim ◽  
Soohyun Wi ◽  
Jung Hwa Seo ◽  
Soonil Pyo ◽  
Sung-Rae Cho
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Environmental Enrichment ◽  
Early Stage ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Close Link ◽  
Non Motor Symptoms

Abstract BackgroundAlthough Parkinson’s disease (PD) is one of the prevalent motor diseases caused by the accumulation of mutated α-Synuclein (α-Syn), it is characterized by non-motor symptoms such as olfactory loss, cognitive decline, depression and anxiety in the early stage of the disease. Environmental enrichment (EE) provides a complex environment comprising physical, cognitive, and social stimuli that improve synaptic plasticity and behavioral functions. The therapeutic effects of EE on behavioral recovery of motor function in a mouse model of PD pathology have been reported. However, the effects of EE on non-motor symptoms in human A53T α-Syn overexpressing transgenic (hA53T α-Syn) mice have yet to be determined. In this study, we revealed the beneficial effect of EE on changes in synaptic plasticity in the striatum and nucleus accumbens (NAc) during the initial phase of PD.MethodTo investigate therapeutic effects of EE in abnormalities during the early phase of PD, we randomly assigned eight-month-old hA53T α-Syn mice to either EE (PD-EE) or standard conditions (PD-SC) for two months. Next, we performed behavioral tests, biochemical and histological analysis at 10 months of age.ResultsEE significantly alleviated locomotor hyperactivity and anxiety in the early stage of PD. EE normalized the level of tyrosine hydroxylase (TH), phosphorylated and oligomeric forms of α-Syn (pSer129 α-Syn), and SNARE complex-forming proteins including SNAP-25, Syntaxin1 and VAMP2. Moreover, the close link between VAMP2 and pSer129 α-Syn was significantly reduced after exposure to EE.ConclusionsOur results showed that EE attenuates aversive mood state on the early stage of PD mouse model. These results were parallel with the reduced expression of pathological α-Syn and the increased expression of neurotransmitter transporter proteins in EE. Interestingly, the interaction between pSer129 α-Syn and VAMP2 also decreased in EE. The restoration of synaptic vesicle transportation status may be responsible for the neuroprotective effects of EE in hA53T α-Syn mice.

scholarly journals Reduced Interaction of Aggregated α-Synuclein and VAMP2 by Environmental Enrichment Alleviates Hyperactivity and Anxiety in a Model of Parkinson’s Disease

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 392
Author(s):  
Kyungri Kim ◽  
Soohyun Wi ◽  
Jung Hwa Seo ◽  
Soonil Pyo ◽  
Sung-Rae Cho
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Enrichment ◽  
Standard Condition ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Early Stages ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a prevalent motor disease caused by the accumulation of mutated α-synuclein (α-Syn); however, its early stages are also characterized by non-motor symptoms, such as olfactory loss, cognitive decline, depression, and anxiety. The therapeutic effects of environmental enrichment (EE) on motor recovery have been reported, but its effects on non-motor symptoms remain unclear. Herein, we reveal the beneficial effects of EE on PD-related non-motor symptoms and changes in synaptic plasticity in the nucleus accumbens. To investigate its therapeutic effects in the early phase of PD, we randomly assigned eight-month-old mice overexpressing human A53T (hA53T) α-Syn to either the EE or standard condition groups for two months. Next, we performed behavioral tests and biochemical and histological analyses at 10 months of age. EE significantly alleviated locomotor hyperactivity and anxiety during the early stages of PD. It normalized the levels of tyrosine hydroxylase, phosphorylated and oligomeric α-Syn, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex-forming proteins, including synaptosomal-associated protein, 25 kDa, syntaxin1, and vesicle-associated membrane protein 2 (VAMP2). Moreover, the interactions between VAMP2 and pSer129 α-Syn were markedly reduced following EE. The restoration of synaptic vesicle transportation status may underlie the neuroprotective effects of EE in hA53T α-Syn mice.

scholarly journals A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Survival Rates ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Operative Care ◽  
6 Hydroxydopamine ◽  
Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

Effects of deep brain stimulation on sleep-wake disturbances in patients with Parkinson's disease: A narrative review

2021 ◽  
Vol 19 ◽  
Author(s):  
Yu Jin Jung ◽  
Han-Joon Kim ◽  
Sun Ha Paek ◽  
Beomseok Jeon
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Early Stage ◽  
Motor Symptoms ◽  
Specific Effects ◽  
The Impact ◽  
Non Motor Symptoms ◽  
Deep Brain

: Sleep-wake disturbances (SWD) are one of the most common non-motor symptoms in Parkinson's disease (PD) and can appear in the early stage even before the onset of motor symptoms. Deep brain stimulation (DBS) is an established treatment for the motor symptoms in patients with advanced PD. However, the effect of DBS on SWD and its specific mechanisms are not widely understood and remain controversial. In addition to the circuit-mediated direct effect, DBS may improve SWD by an indirect effect such as the resolution of nocturnal motor complications and a reduction of dopaminergic medication. Here, the authors review the recent literatures regarding the impact of DBS on SWD in patients with PD. Furthermore, the selection of the DBS targets and the specific effects of applying DBS to each target on SWD in PD are also discussed.

scholarly journals Screening Patients with Early Stage Parkinson’s Disease Using a Machine Learning Technique: Measuring the Amount of Iron in the Basal Ganglia

2020 ◽  
Vol 10 (23) ◽  
pp. 8732
Author(s):  
Seon Lee ◽  
Se-Hong Oh ◽  
Sun-Won Park ◽  
Chaewon Shin ◽  
Jeehun Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Grey Matter ◽  
Early Stage ◽  
Support Vector ◽  
Motor Symptoms ◽  
Model Based ◽  
Svm Model ◽  
Deep Grey Matter ◽  
Non Motor Symptoms

The purpose of this study was to determine whether a support vector machine (SVM) model based on quantitative susceptibility mapping (QSM) can be used to differentiate iron accumulation in the deep grey matter of early Parkinson’s disease (PD) patients from healthy controls (HC) and Non-Motor Symptoms Scale (NMSS) scores in early PD patients. QSM values on magnetic resonance imaging (MRI) were obtained for 24 early PD patients and 27 age-matched HCs. The mean QSM values in deep grey matter areas were used to construct SVM and logistic regression (LR) models to differentiate between early PD patients and HCs. Additional SVM and LR models were constructed to differentiate between low and high NMSS scores groups. A paired t-test was used to assess the classification results. For the differentiation between early PD patients and HCs, SVM had an accuracy of 0.79 ± 0.07, and LR had an accuracy of 0.73 ± 0.03 (p = 0.027). SVM for NMSS classification had a fairly high accuracy of 0.79 ± 0.03, while LR had 0.76 ± 0.04. An SVM model based on QSM offers competitive accuracy for screening early PD patients and evaluates non-motor symptoms, which may offer clinicians the ability to assess the progression of motor symptoms in the patient population.

scholarly journals Longitudinal evolution of non-motor symptoms in early Parkinson’s disease: a 3-year prospective cohort study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ruwei Ou ◽  
Yanbing Hou ◽  
Qianqian Wei ◽  
Junyu Lin ◽  
Kuncheng Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Effect Size ◽  
Rating Scale ◽  
Early Stage ◽  
Chinese Patients ◽  
Sexual Dysfunctions ◽  
Motor Symptoms ◽  
Small Effect Size ◽  
Non Motor Symptoms

AbstractThe progression of global non-motor symptoms (NMS) in Chinese patients with Parkinson’s disease (PD) has not been explored. We aimed to examine the longitudinal evolution of overall NMS in a 3-year prospective Chinese cohort with early-stage PD. We included 224 patients with early PD who underwent annual evaluation of motor and non-motor symptoms. NMS was assessed using the non-motor symptoms scale (NMSS). We observed an increased number of NMS in the majority of the NMSS domains except mood/apathy and sexual dysfunctions. Significant deterioration was observed in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains during the follow-up (P < 0.05). Notably, the number and the score of sexual dysfunctions decreased with the progression of the disease. All NMSS domains showed a small effect size from baseline to 1-, 2-, and 3-year follow-ups (effect size < 0.5). The generalized estimating equations model indicated that the total number of NMS was significantly associated with age and the Unified Parkinson’s Disease Rating Scale (UPDRS) III score (P < 0.05). Multiple logistic regression indicated that a high number of NMS at baseline was associated with a 3-point, a 6-point, and a 9-point increase in the UPDRS III score from baseline to 1-year (odds ratio [OR] 1.074, P = 0.017), 2-year (OR 1.113, P = 0.001), and 3-year (OR 1.117, P < 0.001), respectively. Our study indicated that overall NMS evolution in early PD is mild and multidimensional; a high NMS burden in early PD predicts the faster motor progression of PD. Our study is helpful for understanding the longitudinal evolution of NMS in PD.

scholarly journals Unusual motor and non-motor symptoms and signs in the early stage of Parkinson’s disease

2016 ◽  
Vol 74 (10) ◽  
pp. 781-784 ◽  
Author(s):  
Hélio A. G. Teive ◽  
Délcio C. Bertucci Filho ◽  
Renato P. Munhoz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Shoulder Pain ◽  
Movement Disorders ◽  
Early Stage ◽  
Color Discrimination ◽  
Motor Symptoms ◽  
Non Motor Symptoms ◽  
Symptoms And Signs

ABSTRACT Objective Patients with Parkinson’s disease (PD) may present with unusual motor and non-motor symptoms and signs in the early stage of the disease. Methods Cases were collected over a five-year period at two tertiary movement disorders clinics. All had a diagnosis of PD with unusual presentations defined retrospectively as the presence of complaints not objectively related to any of the classic cardinal signs of parkinsonism or the typical early non-motor features of PD. Results A total of 15 early PD patients fulfilled the proposed criteria, presenting with symptoms such as atypical tremors, shoulder pain, signs related to the rigid akinetic syndrome, as well as cases of asthenia, rhinorrhea, parosmia, dysgeusia, nocturnal sialorrhea, and color discrimination disorders. Conclusions Unusual motor and non-motor symptoms and signs in the early stage of PD can be difficult to interpret. Specialists should be aware of these conditions as clues to a potential diagnosis.

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