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Journal of Neurology, Neurosurgery, and... Mar 2016The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence, rather than the presence, of an imaging abnormality in patients clinically... (Review)
Review
The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence, rather than the presence, of an imaging abnormality in patients clinically presumed to have Parkinson's disease (PD). However, such a term has since been widely used in the medical literature, even as a diagnostic label. While many authors have suggested that different disorders of PD lookalikes may account for a proportion of SWEDD cases, others have claimed that some of them may have a benign subtype of PD. Thus, there has been ensuing controversy and confusion and the use of this term continues without clarity of what it represents. We have systematically reviewed all the studies involving patients with SWEDD with the aim of shedding light on what these patients actually have. It becomes clear from this systematic review that while most 'SWEDD' cases are due to a clinical misdiagnosis of PD, there exists a small proportion of patients with SWEDD who may have PD on the basis of a positive levodopa response, clinical progression, imaging and/or genetic evidence. The latter challenge the seemingly incontrovertible relationship between dopaminergic tracer binding and the diagnosis of nigrostriatal parkinsonism, particularly PD. Patients with SWEDD are unlikely to reflect a single clinical entity and we suggest that the term SWEDD should be abandoned.
Topics: Diagnostic Errors; Dopaminergic Neurons; Functional Neuroimaging; Humans; Parkinson Disease; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 25991401
DOI: 10.1136/jnnp-2014-310256 -
Phytotherapy Research : PTR Jul 2017Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most... (Review)
Review
Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti-apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Disease Models, Animal; Dopamine; Dopamine D2 Receptor Antagonists; Dopaminergic Neurons; Humans; Neuroprotective Agents; Parkinson Disease; Phytotherapy; Plant Extracts
PubMed: 28544038
DOI: 10.1002/ptr.5813 -
Psychiatry Research Nov 2019Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans.
OBJECTIVE
Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans.
METHOD
A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Cochrane Library, Insight and Gray literature (Google Scholar and the British Library) for studies published until August 2018. A search strategy was developed using the terms: "dopamine" and "ethanol" or ""alcohol"," and "positron-emission tomography" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched.
RESULTS
We found 293 studies. After reading titles and abstracts 235 were considered irrelevant, as they did not meet the inclusion criteria. For the reading of the full text, 50 studies were analyzed. Of these 41 were excluded with reasons by study design, patient population, intervention and outcomes. Nine studies were included in our qualitative synthesis. Four studies have resulted in a reduction in availability only at the D2 receptor in different brain regions. Concerning the D3 receptor alone only one study reported this finding and four studies reported a decrease in both receptors.
CONCLUSION
Changes in D2 receptors in several brain regions in human alcoholics were found in a systematic review.
Topics: Alcoholism; Dopamine; Dopaminergic Neurons; Humans; Positron-Emission Tomography; Receptors, Dopamine D2
PubMed: 31521841
DOI: 10.1016/j.psychres.2019.112542 -
Cureus Oct 2022Neurodegenerative diseases, in particular Parkinson's disease (PD), a disabling disorder, require early attention due to the course the diseases take. By the time of... (Review)
Review
Neurodegenerative diseases, in particular Parkinson's disease (PD), a disabling disorder, require early attention due to the course the diseases take. By the time of clinical manifestation, dopaminergic neuron death would have already exceeded a damaging level. Therefore, the discovery of biomarkers that will effectively diagnose PD at an early stage and help monitor disease advancement is crucial. Out of the available biomarkers and bodily sources from which these can be isolated; alpha-synuclein (a-syn) from saliva seems to be a promising and easily accessible option. This has been further investigated in this systematic review. A comprehensive literature search on PubMed, PubMed Central (PMC), and Science Direct resulted in 1,439 articles. After screening and exclusion, 12 relevant articles were derived. In many of the studies, there was a decrease in total salivary a-syn in PD patients compared to healthy controls (HC), with an increase in oligo a-syn and oligo a-syn/total a-syn ratio as a rather consistent finding amongst the studies reviewed. On the other hand, a few studies revealed no significant difference in a-syn levels between the controls and PD patients. Another common finding was the lack of disease severity correlation with the marker, probably due to the scarcity of longitudinal studies conducted and smaller cohorts recruited in the studies. Overall, the total a-syn did show a genetic and phenotypic association, whilst oligo a-syn had the potential to serve as a biomarker for disease diagnosis. With the standardization of sample collection methods and diagnostic tools, and the accomplishment of longitudinal studies, further importance of salivary a-syn as a biomarker in PD could be established, utilizing the already existing data as an encouraging foundation for future research.
PubMed: 36348879
DOI: 10.7759/cureus.29880 -
Frontiers in Neural Circuits 2021The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex...
The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex connections with the other basal ganglia nuclei and brain regions. Recently, with the adoption of sophisticated genetic tools, substantial advances have been made in understanding the distinct molecular, anatomical, electrophysiological, and functional properties of GPe neurons and non-neuronal cells. Impairments in dopamine transmission in the basal ganglia contribute to Parkinson's disease (PD), the most common movement disorder that severely affects the patients' life quality. Altered GPe neuron activity and synaptic connections have also been found in both PD patients and pre-clinical models. In this review, we will summarize the main findings on the composition, connectivity and functionality of different GPe cell populations and the potential GPe-related mechanisms of PD symptoms to better understand the cell type and circuit-specific roles of GPe in both normal and PD conditions.
Topics: Basal Ganglia; Dopamine; Globus Pallidus; Humans; Neurons; Parkinson Disease
PubMed: 33737869
DOI: 10.3389/fncir.2021.645287 -
Frontiers in Aging Neuroscience 2020Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models...
Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models of Parkinson's disease (PD). However, their pooled effects for dopaminergic neuron have yet to be described. To review the neuroprotective effect of naïve BMSCs in rodent models of PD. The PubMed, EMBASE, and Web of Science databases were searched up to September 30, 2020. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified BMSCs; (3) comparison: not specified; (4) primary outcome: tyrosine hydroxylase level in the substantia nigra pars compacta and rotational behavior; secondary outcome: rotarod test, and limb function; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis. Twenty-seven animal studies were included. The median quality score was 4.7 (interquartile range, 2-8). Overall standardized mean difference between animals treated with naïve BMSCs and controls was 2.79 (95% confidence interval: 1.70, 3.87; < 0.001) for densitometry of tyrosine hydroxylase-positive staining; -1.54 (95% confidence interval: -2.11, -0.98; < 0.001) for rotational behavior. Significant heterogeneity among studies was observed. Results of this meta-analysis suggest that naïve BMSCs therapy increased dopaminergic neurons and ameliorated behavioral deficits in rodent models of PD.
PubMed: 33362527
DOI: 10.3389/fnagi.2020.539933 -
Frontiers in Neurology 2020Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra...
Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra (SN). There is also an increase in iron content in the SN in postmortem and imaging studies using iron-sensitive MRI techniques. However, MRI results are variable across studies. We performed a systematic meta-analysis of SN iron imaging studies in PD to better understand the role of iron-sensitive MRI quantification to distinguish patients from healthy controls. We also studied the factors that may influence iron quantification and analyzed the correlations between demographic and clinical data and iron load. We searched PubMed and ScienceDirect databases (from January 1994 to December 2019) for studies that analyzed iron load in the SN of PD patients using T2, R2, susceptibility weighting imaging (SWI), or quantitative susceptibility mapping (QSM) and compared the values with healthy controls. Details for each study regarding participants, imaging methods, and results were extracted. The effect size and confidence interval (CI) of 95% were calculated for each study as well as the pooled weighted effect size for each marker over studies. Hence, the correlations between technical and clinical metrics with iron load were analyzed. Forty-six articles fulfilled the inclusion criteria including 27 for T2/R2 measures, 10 for SWI, and 17 for QSM (3,135 patients and 1,675 controls). Eight of the articles analyzed both R2 and QSM. A notable effect size was found in the SN in PD for R2 increase (effect size: 0.84, 95% CI: 0.60 to 1.08), for SWI measurements (1.14, 95% CI: 0.54 to 1.73), and for QSM increase (1.13, 95% CI: 0.86 to 1.39). Correlations between imaging measures and Unified Parkinson's Disease Rating Scale (UPDRS) scores were mostly observed for QSM. The consistent increase in MRI measures of iron content in PD across the literature using R2, SWI, or QSM techniques confirmed that these measurements provided reliable markers of iron content in PD. Several of these measurements correlated with the severity of motor symptoms. Lastly, QSM appeared more robust and reproducible than R2 and more suited to multicenter studies.
PubMed: 32547468
DOI: 10.3389/fneur.2020.00366 -
Mini Reviews in Medicinal Chemistry 2023Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD),...
BACKGROUND
Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD), Parkinson's disease (PD), Multiple sclerosis, and Amyotrophic lateral sclerosis (ALS). Neurodegenerative diseases (NDs) are indicated by progressive loss of neurons and cognitive function, which is associated with free radical formation, extra and intercellular accumulation of misfolded proteins, oxidative stress, mitochondrial and neurotrophins dysfunction, bioenergetic impairment, inflammation, and apoptotic cell death. Boswellic acid is a pentacyclic triterpene molecule of plant origin that has been applied for treating several inflammatory disorders. Numerous studies have also investigated its' therapeutic potential against multiple NDs.
OBJECTIVE
In this article, we aim to review the neuroprotective effects of boswellic acid on NDs and the related mechanisms of action.
METHODS
The databases of PubMed, Google Scholar, Web of Sciences, and Scopus were searched to find studies that reported the effects of boswellic acid on NDs without time limits. Review articles, letters, editorials, unpublished data, and articles not published in the English language were not included in the study.
RESULTS
Overall, 17 studies were included in the present study (8 NDs in general, 5 AD, 3 PD, and 1 ALS). According to the reports, boswellic acid exerts anti-inflammatory, antioxidant, antiapoptotic, and neuromodulatory effects against NDs. Boswellic acid decreases Tau phosphorylation and amyloid-β (Aβ) generation in AD. This substance also protects nigrostriatal dopaminergic neurons and improves motor impairments in PD and modulates neurotransmitters, decreases the demyelination region, and improves behavioral functions in ALS.
CONCLUSION
Due to the significant effects of boswellic acid in NDs, more clinical studies are necessary to evaluate the pharmacokinetics of this substance because it seems that boswellic acid can be used as a complementary or alternative treatment in patients with NDs.
Topics: Humans; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Alzheimer Disease; Parkinson Disease
PubMed: 36998129
DOI: 10.2174/1389557523666230330113611 -
Metabolites Oct 2018While progress has been made in discerning genetic associations with Parkinson's disease (PD), identifying elusive environmental contributors necessitates the... (Review)
Review
While progress has been made in discerning genetic associations with Parkinson's disease (PD), identifying elusive environmental contributors necessitates the application of unconventional hypotheses and experimental strategies. Here, we provide an overview of studies that we conducted on a neurotoxic metabolite produced by a species of common soil bacteria, ), indicating that the toxicity displayed by this bacterium causes stress in diverse cellular mechanisms, such as the ubiquitin proteasome system and mitochondrial homeostasis. This dysfunction eventually leads to age and dose-dependent neurodegeneration in the nematode . Notably, dopaminergic neurons have heightened susceptibility, but all of the neuronal classes eventually degenerate following exposure. Toxicity further extends to human SH-SY5Y cells, which also degenerate following exposure. Additionally, the neurons of nematodes expressing heterologous aggregation-prone proteins display enhanced metabolite vulnerability. These mechanistic analyses collectively reveal a unique metabolomic fingerprint for this bacterially-derived neurotoxin. In considering that epidemiological distinctions in locales influence the incidence of PD, we surveyed soils from diverse regions of Alabama, and found that exposure to ~30% of isolated species caused worm dopaminergic neurons to die. In addition to aging, one of the few established contributors to PD appears to be a rural lifestyle, where exposure to soil on a regular basis might increase the risk of interaction with bacteria producing such toxins. Taken together, these data suggest that a novel toxicant within the genus might represent an environmental contributor to the progressive neurodegeneration that is associated with PD.
PubMed: 30380609
DOI: 10.3390/metabo8040070 -
Ageing Research Reviews May 2018To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in...
OBJECTIVE
To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD).
METHODS
Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate.
RESULTS
Forty-five studies were included. Monoamines (serotonin, dopamine and noradrenaline) were most commonly investigated. A variety of methods were used to investigate the neurochemistry underlying agitation in AD and, although there were several conflicting findings, there was evidence of serotonergic deficit, relatively preserved dopaminergic function and compensatory overactivity of postsynaptic noradrenergic neurons in agitation in AD.
CONCLUSIONS
Disruption of the dynamic balance between multiple neurotransmitter systems could impair functional neural networks involved in affective regulation and executive function. Differences in study design and methodology may have contributed to conflicting findings. Future studies that overcome these limitations (e.g. using standardized criteria to define agitation) and employ neuroimaging methods such as MRI/PET to investigate specific neural networks are needed to clarify the role of neurotransmitter alterations in these patients.
Topics: Alzheimer Disease; Brain Chemistry; Dopamine; Humans; Neurochemistry; Neurotransmitter Agents; Psychomotor Agitation
PubMed: 29524596
DOI: 10.1016/j.arr.2018.03.003