scholarly journals A mouse model of non-motor symptoms in Parkinson's disease: focus on pharmacological interventions targeting affective dysfunctions

2014 ◽  
Vol 8 ◽  
Author(s):  
Alessandra Bonito-Oliva ◽  
Débora Masini ◽  
Gilberto Fisone
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Motor Symptoms ◽  
Pharmacological Interventions ◽  
Non Motor Symptoms ◽  
Disease Focus

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.

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 The Parkinson’s Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson’s Disease in Patients and their Carers

2021 ◽  
pp. 1-15
Author(s):  
Eduardo Tolosa ◽  
Georg Ebersbach ◽  
Joaquim J. Ferreira ◽  
Olivier Rascol ◽  
Angelo Antonini ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impact Assessment ◽  
Real World ◽  
European Countries ◽  
Life Questionnaire ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8% . Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.

scholarly journals Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Hamdy N. El-Tallawy ◽  
Tahia H. Saleem ◽  
Wafaa M. Farghaly ◽  
Heba Mohamed Saad Eldien ◽  
Ashraf Khodaery ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Motor Symptoms ◽  
And Control ◽  
Non Motor Symptoms ◽  
Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

scholarly journals Weeding through the haze: a survey on cannabis use among people living with Parkinson’s disease in the US

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Megan P. Feeney ◽  
Danny Bega ◽  
Benzi M. Kluger ◽  
A. Jon Stoessl ◽  
Christiana M. Evers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Scientific Evidence ◽  
Symptom Control ◽  
Cannabis Use ◽  
Symptom Improvement ◽  
Motor Symptoms ◽  
The Us ◽  
Alternative Means ◽  
Non Motor Symptoms

AbstractSymptomatic management of Parkinson’s disease (PD) is complex and many symptoms, especially non-motor symptoms, are not effectively addressed with current medications. In the US, cannabis has become more widely available for medical and recreational use, permitting those in the PD community to try alternative means of symptom control. However, little is known about the attitudes towards, and experiences with, cannabis use among those living with PD. To address this shortcoming, we distributed an anonymous survey to 7,607 people with PD in January 2020 and received 1339 responses (17.6%). 1064 complete responses were available for analysis. Respondents represented 49 states with a mean age of 71.2 years (±8.3) and mean PD duration of 7.4 years (±6.2). About a quarter of respondents (24.5%) reported cannabis use within the previous six months. Age and gender were found to be predictors of cannabis use in this sample (Age OR = 0.95, 95% CI 0.93 to 0.97; Male OR = 1.44, 95% CI 1.03 to 2.03). Users reported learning about cannabis use from the internet/news (30.5%) and friends or other people with PD (26.0%). Cannabis users were more likely to report insufficient control of their non-motor symptoms with prescription medications than non-users (p = 0.03). Cannabis was primarily used for PD (63.6%) and was most often used to treat nonmotor symptoms of anxiety (45.5%), pain (44.0%), and sleep disorders (44.0%). However, nearly a quarter of users (23.0%) also reported they had stopped cannabis use in the previous six months, primarily due to a lack of symptom improvement (35.5%). Three quarters of respondents (75.5%) did not use cannabis, primarily because there was a lack of scientific evidence supporting efficacy (59.9%). Our results suggest that the lack of formal guidance or research evidence about cannabis for PD may in part underlie inconsistencies in both use and reported effectiveness.

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