scholarly journals Human α-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy

2021 ◽  
Author(s):  
Analia Bortolozzi ◽  
Lluis Miquel-Rio ◽  
Diana Alarcón-Aris ◽  
María Torres-López ◽  
Valentín Coppola-Segovia ◽  
...  
Keyword(s):  
Negative Impact ◽  
Neuropsychiatric Symptoms ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Bdnf Expression ◽  
Adeno Associated Virus ◽  
Serotonin Neurons ◽  
Progressive Accumulation ◽  
Premotor Phase

Abstract Anxiety and depression affect 35–50% of patients with Parkinson's disease (PD), often precede the onset of motor symptoms, and have a negative impact on their quality of life. Dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD and contributes to a variety of non-motor symptoms. Furthermore, α-synuclein (α-Syn) aggregates were identified in raphe nuclei in the early stages of the disease. However, there are very few animal models of PD-related neuropsychiatric disorders. Here, we develop a new mouse model of α-synucleinopathy in the 5-HT system that mimics prominent histopathological and neuropsychiatric features of human PD. We showed that adeno-associated virus (AAV5)-induced overexpression of wild-type human α-Syn (h-α-Syn) in raphe 5-HT neurons triggers progressive accumulation, phosphorylation, and aggregation of h-α-Syn protein in the 5-HT system. Specifically, AAV5-injected mice displayed axonal impairment in the output brain regions of raphe neurons, and deficits in brain-derived neurotrophic factor (BDNF) expression and 5-HT neurotransmission, resulting in a depressive-like phenotype. Intracerebroventricular treatment with an indatraline-conjugated antisense oligonucleotide (IND-ASO) for four weeks induced an effective and safe reduction of h-α-Syn synthesis in 5-HT neurons and its accumulation in the forebrain, alleviating early deficits of 5-HT function and improving the behavioural phenotype. Altogether, our findings show that α-synucleinopathy in 5-HT neurons negatively affects brain circuits that control mood and emotions, resembling the expression of neuropsychiatric symptoms occurring at the onset of PD. Early preservation of 5-HT function by reducing α-Syn synthesis/accumulation may alleviate PD-related depressive symptoms.

Parkinsonism, Parkinson’s disease, and related conditions

2017 ◽  
pp. 897-906
Author(s):  
John V. Hindle ◽  
Sion Jones ◽  
Glesni Davies
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older People ◽  
Lewy Bodies ◽  
Cell Loss ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Advanced Care Planning ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a progressive neurodegenerative condition characterized clinically by fatiguable bradykinesia, rigidity and tremor and pathologically by deposition of Lewy bodies and cell loss in the substantia nigra and other brain regions. Parkinsonism is the term used to describe the clinical features of conditions resembling PD. Their management requires specialist assessment and a multidisciplinary approach. Levodopa remains the mainstay of treatment for PD. Although other treatments are used, older people are more sensitive to their side effects. Non-motor symptoms, particularly neuropsychiatric problems, significantly impact quality of life and need special consideration in older people. Towards the later stage of the disease, management can be complex, and should involve advanced care planning.

scholarly journals Neurobiology of Depression and Anxiety in Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Osamu Kano ◽  
Ken Ikeda ◽  
Derek Cridebring ◽  
Takanori Takazawa ◽  
Yasuhiro Yoshii ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Features ◽  
Motor Symptoms ◽  
Depression And Anxiety ◽  
Neurochemical Changes ◽  
Premotor Phase

Depression and anxiety are common in Parkinson's disease (PD) and have important consequences on quality of life. These have long been recognized as frequent accompanying syndromes of PD, and several reports suggest that these are the causative process or risk factors that are present many years before the appearance of motor symptoms. The neurochemical changes in PD involving dopamine, norepinephrine, and serotonin might be related to the pathophysiology of depression and anxiety, but this is still not clear. Several studies showed that anxiety in PD patients occurs earlier than depression, during premotor phase, suggesting that there may be a link between the mechanisms that cause anxiety and PD. Whereas a recent study reported that PD patients with depression and anxiety were associated with different demographic and clinical features.

scholarly journals Effect of Olfactory and Gustatory Dysfunction and Motor Symptoms on Body Weight in Patients with Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 218
Author(s):  
Carla Masala ◽  
Francesco Loy ◽  
Raffaella Piras ◽  
Anna Liscia ◽  
Laura Fadda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Rating Scale ◽  
Negative Impact ◽  
Motor Symptoms ◽  
Weight Regulation ◽  
Disease Rating ◽  
Non Motor Symptoms

Background: Non-motor symptoms in Parkinson’s disease (PD) are often associated with a negative impact on the patients’ quality of life and on their weight regulation. The aim of this study was to assess the effect of olfactory and gustatory dysfunction, apathy, fatigue, depression, and motor symptoms on weight regulation in PD patients. Methods: We analyzed 112 participants, 63 PD patients (mean age ± SD: 69.2 ± 10.1), and 49 controls (mean age ± SD: 68 ± 9.6). For each participant we collected age, weight, height, BMI, olfactory and gustatory function, cognitive performance, apathy and fatigue. Results: Our data showed that 61.9% (n = 39) of PD patients had hyposmia, while 38.1% (n = 24) had anosmia. In PD patients, we observed a significant effect of Unified Parkinson’s Disease Rating Scale (UPDRS), apathy, odor threshold, sweet perception and fatigue on weight regulation. Instead, there was no significant effect for depression and levodopa equivalent daily dosage (LEDD). Conclusion: Our results suggest that PD non-motor symptoms such as olfactory/gustatory deficits and mood disorders may influence body weight.

scholarly journals Influence of Mild Cognitive Impairment, Depression, and Anxiety on the Quality of Life of Patients with Parkinson Disease

2017 ◽  
Vol 7 (3) ◽  
pp. 297-308 ◽  
Author(s):  
Daniel Wiesli ◽  
Antonia Meyer ◽  
Peter Fuhr ◽  
Ute Gschwandtner
Keyword(s):  
Quality Of Life ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Linear Regression ◽  
Parkinson Disease ◽  
Negative Impact ◽  
Neuropsychiatric Symptoms ◽  
Self Report ◽  
Minor Importance

Background: Neuropsychiatric symptoms (NPS) and mild cognitive impairment (MCI) are common in Parkinson disease (PD) and have a negative impact on the patient’s quality of life (QoL). We aim to describe the effect of NPS and MCI on each other and on QoL. Methods: Sixteen MCI and 37 non-MCI PD patients completed different self-assessment questionnaires including the Parkinson’s Disease Questionnaire (PDQ-39), the Beck Depression Inventory (BD), the Beck Anxiety Inventory (BAI), and the Self-Report Manic Inventory (SRMI). Linear regression with stepwise elimination was used to select the significant predictors of QoL and to control for confounding factors. Results: The significant linear regression model (R2 = 0.68, p ≤ 0.01) revealed significant effects of MCI (p = 0.03), BDI (p ≤ 0.01), BAI (p ≤ 0.01), age (p = 0.03), a trend of SRMI (p = 0.06), and disease duration (p = 0.08) on QoL. Conclusions: MCI, anxiety, depression, and age decrease QoL in patients with PD. NPS has the main influence in the prediction of QoL in patients with PD, whereas MCI is only of minor importance.

Musical Anhedonia

2020 ◽  
Vol 31 (2) ◽  
pp. 62-68
Author(s):  
Sara E. Holm ◽  
Alexander Schmidt ◽  
Christoph J. Ploner
Keyword(s):  
Quality Of Life ◽  
Nucleus Accumbens ◽  
Brain Damage ◽  
Parietal Cortex ◽  
Neurological Disorders ◽  
Brain Regions ◽  
Precise Information ◽  
Exact Localization ◽  
High Prevalence

Abstract. Some people, although they are perfectly healthy and happy, cannot enjoy music. These individuals have musical anhedonia, a condition which can be congenital or may occur after focal brain damage. To date, only a few cases of acquired musical anhedonia have been reported in the literature with lesions of the temporo-parietal cortex being particularly important. Even less literature exists on congenital musical anhedonia, in which impaired connectivity of temporal brain regions with the Nucleus accumbens is implicated. Nonetheless, there is no precise information on the prevalence, causes or exact localization of both congenital and acquired musical anhedonia. However, the frequent involvement of temporo-parietal brain regions in neurological disorders such as stroke suggest the possibility of a high prevalence of this disorder, which leads to a considerable reduction in the quality of life.

Green Beans Cultivation Using Mice Pets Control to Improve the Quality of Bintaro Fruit Extract

2018 ◽  
Vol 1 (1) ◽  
pp. 38
Author(s):  
Ajeng Embri Legawati ◽  
Nur Azizah ◽  
Achmad Ramadhan
Keyword(s):  
Natural Resources ◽  
Negative Impact ◽  
Green Beans ◽  
Fruit Extract ◽  
Bean Plants ◽  
Cultivation Technology ◽  
Environmental Balance ◽  
The Impact ◽  
Chemical Pesticides

Green beans cultivation technology using mice pets control has been implemented in the Gluranploso village, Benjeng Gresik. The implementation of the technology performed for 2.5 months from August to October 2017. The purpose of the implementation is aimed to reduce the dependence of farmers on the use of chemical pesticides so that the farmers are aware of the negative impact of chemical pesticides. Assessing the impact of the utilization of Bintaro fruit and fruit extracts to explore ways of making Bintaro as a natural biopesticide to overcome rat attack on green bean plants in the Gluranploso village. Pest control mice can reduce the rate of loss of the crops more effectively and efficiently. Finally, with the use of those natural resources as a biopesticide material can also maintain the environmental balance

CHRONOBIOLOGICAL AND PSYCHOEMOTIONAL STATUS IN WOMEN WITH CHRONIC RECURRENT BACTERIAL CYSTITIS AND CARBOHYDRATE METABOLISM DISORDER

2020 ◽  
pp. 56-59
Author(s):  
Мария Николаевна Химичева ◽  
Андрей Владимирович Кузьменко ◽  
Владимир Васильевич Кузьменко ◽  
Тимур Асланбекович Гяургиев
Keyword(s):  
Chronic Disease ◽  
Carbohydrate Metabolism ◽  
Negative Impact ◽  
High Risk Group ◽  
Chronic Complications ◽  
Course Of Disease ◽  
Metabolism Disorder ◽  
Common Group ◽  
Tract Infections

Инфекции мочевых путей - наиболее распространённая группа заболеваний в практике врача уролога. Один из представителей является хронический рецидивирующий бактериальный цистит. Данное заболевание встречается во всех возрастных категориях и затрагивает все сферы жизни пациентов. Симптомы, возникающие при обострении хронического бактериального цистита, оказывают негативное влияние на качество жизни, что может приводить к нарушению психоэмоционального состояния больных. Отдельную группу высокого риска в отношении ИНМП составляют пациенты с нарушением углеводного обмена, у которых риск развития различных инфекций выше, чем у людей без подобных нарушений. К факторам, повышающим риск развития ИНМП у больных с нарушением углеводного обмена, относят возраст, компенсацию и наличие хронических осложнений, в первую очередь нефропатии и цистопатии. Человеческий организм функционирует циклически в соответствии с определенными индивидуальными ритмами. Любое хроническое заболевание приводит к рассогласованию процессов, протекающих в различных системах организма, вызывая развитие десинхроноза. Наличие у человека более 1 хронического заболевания утяжеляет течение болезни и приводит к снижению восстановительных способностей организма и сокращению его адаптационного потенциала Urinary tract Infections are the most common group of diseases in the practice of a urologist. One of the representatives is chronic recurrent bacterial cystitis. This disease occurs in all age categories and affects all areas of life of patients. Symptoms that occur with the exacerbation of chronic bacterial cystitis have a negative impact on the quality of life, which can lead to a violation of the psychoemotional state of patients. A separate high-risk group for INMP is patients with impaired carbohydrate metabolism, who have a higher risk of developing various infections than people without such disorders. Factors that increase the risk of developing INMP in patients with impaired carbohydrate metabolism include age, compensation, and the presence of chronic complications, primarily nephropathy and cystopathy. The human body functions cyclically in accordance with certain individual rhythms. Any chronic disease leads to misalignment of the processes occurring in various body systems, causing the development of DS, the Presence of more than 1 chronic disease complicates the course of disease and leads to a decrease in regenerative abilities of the organism and reduce its adaptive capacity

Modern challenges of border areas development in the context of decentralization reform

2019 ◽  
pp. 79-89
Author(s):  
Khrystyna Prytula ◽  
Yaroslava Kalat ◽  
Iryna Kyryk
Keyword(s):  
Ethnic Minorities ◽  
Negative Impact ◽  
Local Development ◽  
Economic Security ◽  
Uneven Development ◽  
Scientific Article ◽  
Border Regions ◽  
Border Areas ◽  
Decentralization Reform

An integral part of the implementation of any reform is the emergence of the risks of its negative impact on one or another area of region development. The decentralization reform in Ukraine is not an exception. In its the context the most probable occurrence of negative phenomena is in the border regions, which could be prevented by first detecting them. In the scientific article, the authors focus on the analysis of a number of challenges for the development of border regions in the context of decentralization reform. Given the territorial remoteness of the central regions of the country and the capital, which today serve as areas of concentration of investment and economic activity, the border regions traditionally (this is typical for the border areas of the EU member states) lag behind the rest of the regions by the main socio-economic indicators of development. Among the main challenges facing the border regions of Ukraine today are the following: the provision of competitiveness in the context of European integration processes and reduction of the border barrier function; low level of economic security; the outflow of human capital and the issue of ethnic minorities. Based on an expert survey of representatives of the fifteen united territorial communities (UTCs), the possibility of such risks of decentralization in the border regions were defined as following: groundless use of local budget funds; emergence of significant imbalances between delegated new authority and available financial resources of the community; increasing uneven development of territories within the community; increasing uneven development of communities within the country; deterioration of the availability and quality of providing educational and medical services; deterioration of the quality of local government; reducing of the state influence on the management of local development processes; radicalization of political unions representing the interests of ethnic minorities in places of their compact residence; further economic decline of the territory of communities and so on.

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.

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