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Movement Disorders : Official Journal... Jun 2024
PubMed: 38940474
DOI: 10.1002/mds.29892 -
ELife Jun 2024Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these...
Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
Topics: Animals; Dopaminergic Neurons; Serotonergic Neurons; Dorsal Raphe Nucleus; Mice; Disease Models, Animal; Oxidopamine; Parkinsonian Disorders; Male; Mice, Inbred C57BL; Desipramine; Norepinephrine
PubMed: 38940422
DOI: 10.7554/eLife.90278 -
Journal of Integrative Neuroscience May 2024The objective of this study is to compare the differences in effective connectivity within the default mode network (DMN) subsystems between patients with Parkinson's...
OBJECTIVE
The objective of this study is to compare the differences in effective connectivity within the default mode network (DMN) subsystems between patients with Parkinson's disease with mild cognitive impairment (PD-MCI) and patients with Parkinson's disease with normal cognition (PD-CN). The mechanisms underlying DMN dysfunction in PD-MCI patients and its association with clinical cognitive function in PD-MCI are aimed to be investigated.
METHODS
The spectral dynamic causal model (spDCM) was employed to analyze the effective connectivity of functional magnetic resonance imaging (fMRI) data in the resting state for the DMN subsystems, which include the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), left and right angular gyrus (LAG, RAG) in 23 PD-MCI and 22 PD-CN patients, respectively. The effective connectivity values of DMN subsystems in the two groups were statistically analyzed using a two-sample -test. The Spearman correlation analysis was used to test the correlation between the effective connectivity values of the subsystems with significant differences between the two groups and the clinical cognitive function (as measured by Montreal Cognitive Assessment Scale (MoCA) score).
RESULTS
Statistical analysis revealed significant differences in the effective connections of MPFC-LAG and LAG-PCC between the two patient groups (MPFC-LAG: t = -2.993, < 0.05; LAG-PCC: t = 2.174, < 0.05).
CONCLUSIONS
The study findings suggest that abnormal strength and direction of effective connections between DMN subsystems are found in PD-MCI patients.
Topics: Humans; Parkinson Disease; Cognitive Dysfunction; Male; Female; Default Mode Network; Magnetic Resonance Imaging; Aged; Middle Aged; Prefrontal Cortex; Gyrus Cinguli; Connectome; Nerve Net
PubMed: 38940086
DOI: 10.31083/j.jin2306110 -
Journal of Integrative Neuroscience May 2024Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain and the formation of intracellular protein aggregates known as Lewy bodies, of which a major component is the protein α-synuclein. Several studies have suggested that mitochondria play a central role in the pathogenesis of PD, encompassing both familial and sporadic forms of the disease. Mitochondrial dysfunction is attributed to bioenergetic impairment, increased oxidative stress, damage to mitochondrial DNA, and alteration in mitochondrial morphology. These alterations may contribute to improper functioning of the central nervous system and ultimately lead to neurodegeneration. The perturbation of mitochondrial function makes it a potential target, worthy of exploration for neuroprotective therapies and to improve mitochondrial health in PD. Thus, in the current review, we provide an update on mitochondria-based therapeutic approaches toward α-synucleinopathies in PD.
Topics: Humans; Parkinson Disease; Synucleinopathies; Mitochondria; Animals; alpha-Synuclein
PubMed: 38940084
DOI: 10.31083/j.jin2306109 -
Journal of Integrative Neuroscience Jun 2024Deep brain stimulation (DBS) is a common therapy for managing Parkinson's disease (PD) in clinical practice. However, a complete understanding of its mode of action is... (Review)
Review
Deep brain stimulation (DBS) is a common therapy for managing Parkinson's disease (PD) in clinical practice. However, a complete understanding of its mode of action is still needed. DBS is believed to work primarily through electrical and neurochemical pathways. Furthermore, DBS has other mechanisms of action. This review explores the fundamental concepts and applications of DBS in treating PD, including its mechanisms, clinical implications, and recent research.
Topics: Deep Brain Stimulation; Parkinson Disease; Humans; Brain; Animals
PubMed: 38940083
DOI: 10.31083/j.jin2306114 -
Frontiers in Bioscience (Scholar... Jun 2024Several inherited metabolic fatty acid disorders present with myopathies. Skeletal muscle accounts for 40% of the body and is important for metabolism, exercise, and... (Review)
Review
Several inherited metabolic fatty acid disorders present with myopathies. Skeletal muscle accounts for 40% of the body and is important for metabolism, exercise, and movement. Muscle energy failure is manifested by metabolic crises with muscle weakness, sometimes associated with muscle fatigue and failure resulting in acute necrosis or rhabdomyolysis/myoglobinuria episodes. Lack of energy leads to muscle necrosis. Other presentations are weakness and myalgias with lipid storage myopathies in the biopsy. The biomarkers of such disorders are acyl-carnitine with various profiles and need to be carefully evaluated to plan supplementary therapy and specific diets. If red flags are not distinctly followed and diagnosed in time they might lead to a metabolic or cardiac failure.
Topics: Humans; Muscular Diseases; Carnitine; Lipid Metabolism, Inborn Errors; Muscle, Skeletal; Muscular Dystrophies
PubMed: 38939976
DOI: 10.31083/j.fbs1602012 -
Journal of Extracellular Biology Nov 2023Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive... (Review)
Review
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta-analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta-analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta-analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim-and-fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF-EVs showed better overall diagnostic accuracy, while plasma-EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS-originating EVs, which are more time-consuming, labour- and cost-intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV-related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.
PubMed: 38939363
DOI: 10.1002/jex2.121 -
Journal of Extracellular Biology Jan 2024The receptor tyrosine kinase (RTK) KIT and its ligand stem cell factor (SCF) are essential for human mast cell (huMC) survival and proliferation. HuMCs expressing...
The receptor tyrosine kinase (RTK) KIT and its ligand stem cell factor (SCF) are essential for human mast cell (huMC) survival and proliferation. HuMCs expressing oncogenic KIT variants secrete large numbers of extracellular vesicles (EVs). The role KIT plays in regulating EV secretion has not been examined. Here, we investigated the effects of stimulation or inhibition of KIT activity on the secretion of small EVs (sEVs). In huMCs expressing constitutively active KIT, the quantity and quality of secreted sEVs positively correlated with the activity status of KIT. SCF-mediated stimulation of KIT in huMCs or murine MCs, or of transiently expressed KIT in HeLa cells, enhanced the release of sEVs expressing exosome markers. In contrast, ligand-mediated stimulation of the RTK EGFR in HeLa cells did not affect sEV secretion. The release of sEVs induced by either constitutively active or ligand-activated KIT was remarkably decreased when cells were treated with KIT inhibitors, concomitant with reduced exosome markers in sEVs. Similarly, inhibition of oncogenic KIT signalling kinases like PI3K, and MAPK significantly reduced the secretion of sEVs. Thus, activation of KIT and its early signalling cascades stimulate the secretion of exosome-like sEVs in a regulated fashion, which may have implications for KIT-driven functions.
PubMed: 38938682
DOI: 10.1002/jex2.139 -
Innovations in Clinical Neuroscience 2024Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
INTRODUCTION
Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
OBJECTIVE
With new evidence suggesting a link between low high-density lipoprotein cholesterol (HDL-C) and risk of Parkinson's disease, this study sought to investigate if that link also translated to patients taking antipsychotics with low HDL-C and an increased risk for developing a movement disorder.
DESIGN
Adult patients (n=89) at an inpatient state psychiatric facility taking at least one antipsychotic with at least one HDL-C level were assessed for signs of a movement disorder through their history and physical, progress notes, and Abnormal Involuntary Movement Scale (AIMS) score.
RESULTS
There was no statistical significance when comparing a patient's movement disorder, AIMS scores, and HDL-C levels to suggest that the HDL-C level influenced a patient's movement disorder.
CONCLUSION
This study did not show a correlation between HDL-C levels and a patient's risk of developing a movement disorder while taking an antipsychotic.
PubMed: 38938537
DOI: No ID Found -
Frontiers in Human Neuroscience 2024Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating...
INTRODUCTION
Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT).
METHODS
The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings.
RESULTS
Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group.
DISCUSSION
Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.
PubMed: 38938290
DOI: 10.3389/fnhum.2024.1395827