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European Journal of Pharmacology Jun 2024Bitter taste receptors (TAS2Rs) and their downstream signaling pathways are expressed not only in the oral tissues but also in extraoral tissues. Emerging data has...
AIMS
Bitter taste receptors (TAS2Rs) and their downstream signaling pathways are expressed not only in the oral tissues but also in extraoral tissues. Emerging data has demonstrated the beneficial effect of ghrelin in neurodegenerative diseases. Gaining more insight into the interaction between TAS2Rs and gut hormones may expand their therapeutic applications. Herein, we aimed to assess the possible effect of TAS2R activation by denatonium benzoate (DB) in modulating functional and neurobiochemical alterations in a model of Parkinson's disease (PD).
MAIN METHODS
PD model was induced by daily injection of rotenone (2 mg/kg). Rats received DB (5 mg/kg), atenolol (10 mg/kg), or both concomitantly with rotenone, daily for 28 days. Evaluation of the motor abnormalities and histological examination of brain tissues were conducted. In addition, striatal dopamine contents, immunohistochemical expression of tyrosine hydroxylase, plasma ghrelin level, and biochemical analysis of markers of inflammation and oxidative stress were assessed.
KEY FINDINGS
Treatment with DB increased serum levels of ghrelin and striatal dopamine contents with consequent amelioration of oxidative stress and attenuation of inflammatory cytokines. Moreover, DB treatment significantly ameliorated motor disturbance and histological abnormalities compared to untreated rats. Atenolol inhibited ghrelin release and abolished the positive effect of DB suggesting the involvement of ghrelin on such effects.
SIGNIFICANCE
The current study suggests that TAS2Rs agonists are promising candidates for ameliorating rotenone-induced PD pathology in rats, an action that could be linked to the enhancement of ghrelin release with consequent antioxidant and anti-inflammatory activities.
PubMed: 38945288
DOI: 10.1016/j.ejphar.2024.176802 -
Journal of Movement Disorders Jun 2024
Potential Psychosis Induced by Sustained High Plasma Levodopa Concentration via Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in Parkinson's Disease: A Case Report.
PubMed: 38945151
DOI: 10.14802/jmd.24114 -
The Lancet. Healthy Longevity Jul 2024Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's disease, temporal trends between 1980 and 2023, and variations in prevalence by location, age, sex, survey period, sociodemographic index (SDI), human development index (HDI), and study characteristics (sample size, diagnostic criteria, and data source).
METHODS
In this systematic review and meta-analysis we searched PubMed, Cochrane, Web of Science, Embase, Scopus, and Global Health for observational studies that reported Parkinson's disease prevalence in the general population from database inception to Nov 1, 2023. We included studies if they were original observational investigations, had participants from the general population or community-based datasets, and provided numerical data on the prevalence of Parkinson's disease either with 95% CIs or with sufficient information to calculate 95% CIs. Studies were excluded if they were conducted in a specific population, had a sample size smaller than 1000, or were review articles, case reports, protocols, meeting abstracts, letters, comments, short communications, posters, and reports. The publication characteristics (first author and publication year), study location (countries, WHO regions, SDI, and HDI), survey period, study design, diagnostic criteria, data source, participant information, and prevalence data were extracted from articles using a standard form. Two authors independently evaluated eligibility, and discrepancies were resolved through discussion with the third author. We used random effect models to pool estimates with 95% CIs. Estimated annual percentage change (EAPC) was calculated to assess the temporal trend in prevalence of Parkinson's disease. The study was registered with PROSPERO, CRD42022364417.
FINDINGS
83 studies from 37 countries were eligible for analysis, with 56 studies providing all-age prevalence, 53 studies reporting age-specific prevalence, and 26 studies providing both all-age and age-specific prevalence. Global pooled prevalence of Parkinson's disease was 1·51 cases per 1000 (95% CI 1·19-1·88), which was higher in males (1·54 cases per 1000 [1·17-1·96]) than in females (1·49 cases per 1000 [1·12-1·92], p=0·030). During different survey periods, the prevalence of Parkinson's disease was 0·90 cases per 1000 (0·48-1·44; 1980-89), 1·38 cases per 1000 (1·17-1·61; 1990-99), 1·18 cases per 1000 (0·77-1·67; 2000-09), and 3·81 cases per 1000 (2·67-5·14; 2010-23). The EAPC of Parkinson's disease prevalence was significantly higher in the period of 2004-23 (EAPC 16·32% [95% CI 6·07-26·58], p=0·0040) than in the period of 1980-2003 (5·30% [0·82-9·79], p=0·022). Statistically significant disparities in prevalence were observed across six WHO regions. Prevalence increased with HDI or SDI. Considerable variations were observed in the pooled prevalence of Parkinson's disease based on different sample sizes or diagnostic criteria. Prevalence also increased with age, reaching 9·34 cases per 1000 (7·26-11·67) among individuals older than 60 years.
INTERPRETATION
The global prevalence of Parkinson's disease has been increasing since the 1980s, with a more pronounced rise in the past two decades. The prevalence of Parkinson's disease is higher in countries with higher HDI or SDI. It is necessary to conduct more high-quality epidemiological studies on Parkinson's disease, especially in low SDI countries.
FUNDING
National Nature Science Foundation of China.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Parkinson Disease; Humans; Prevalence; Female; Male; Global Health
PubMed: 38945129
DOI: 10.1016/S2666-7568(24)00094-1 -
Mymensingh Medical Journal : MMJ Jul 2024Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease with unknown etiology. Some previous studies suggest that elevated serum homocysteine level...
Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease with unknown etiology. Some previous studies suggest that elevated serum homocysteine level is a risk factor for stroke, ischemic heart disease; atherosclerosis and neurodegenerative diseases like Parkinson's disease. Serum homocysteine level relates with Parkinson's disease through various mechanisms including gene defect, apoptosis, oxidative stress and DNA damage. Some recent studies reveal that serum homocysteine level is elevated in Parkinson's disease patient compared to healthy individuals. This study was aimed to compare the serum homocysteine level in Parkinson's disease patients and age and sex matched apparently healthy individuals. This was a case control study which was conducted in Department of Neurology and Medicine, Mymensingh Medical College Hospital, Mymensingh during November 2019 to April 2021. Total 55 cases of Parkinson's disease patients and age and sex matched 55 apparently healthy controls were enrolled in this study. Demographics and clinical data were collected using structured case record form and adopting purposive type of sampling method. Serum homocysteine level was measured in both case and control groups. The study reveals that, average age of the patients and control group was in sixth decade. Male predominance was found with male to female ratio was 1.5:1 in case group. Both groups showed almost similar demographic profiles. Twenty-nine (52.72%) patients of Parkinson's disease observed higher serum homocysteine level in contrast to only 8(14.54%) in control group. The mean serum homocysteine ±SD was 15.43±6.04μmol/L in case group and 10.04±5.31μmol/L in control group; the difference was statistically significant (p=0.001). Mean serum homocysteine levels were measured progressively higher with increased duration and advanced stages of disease. It was concluded that, serum homocysteine level is higher in Parkinson's disease patients than normal healthy individuals. In addition, there was significant positive correlation of elevated serum homocysteine with increased duration of Parkinson's disease and advanced stages of the disease.
Topics: Humans; Homocysteine; Parkinson Disease; Male; Female; Case-Control Studies; Middle Aged; Aged; Adult; Risk Factors
PubMed: 38944701
DOI: No ID Found -
Thoracic Surgery Clinics Aug 2024
Topics: Humans; Thoracic Surgery; Achievement; Thoracic Surgical Procedures
PubMed: 38944459
DOI: 10.1016/j.thorsurg.2024.05.001 -
Thoracic Surgery Clinics Aug 2024Cardiothoracic surgeons work in high-intensity environments starting in surgical training and throughout their careers. They deal with critical patients. Their routine... (Review)
Review
Cardiothoracic surgeons work in high-intensity environments starting in surgical training and throughout their careers. They deal with critical patients. Their routine procedures are delicate, require extensive attention to detail, and can have detrimental effects on patients' lives. Cardiothoracic surgeons are required to perform at their best capacity incessantly. To do this, they must safeguard their mental and physical well-being. Preserving health through sleep, nutrition, exercise, and routine medical checkups ensures a cardiothoracic surgeon's well-being. Great personal effort and discipline is required to maintain health in a busy schedule. We offer our best recommendations from expert peers in the field.
Topics: Humans; Sleep; Nutritional Status; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Thoracic Surgery; Exercise
PubMed: 38944448
DOI: 10.1016/j.thorsurg.2024.04.004 -
Mitochondrion Jun 2024Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein... (Review)
Review
Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.
PubMed: 38944367
DOI: 10.1016/j.mito.2024.101926 -
Experimental Neurology Jun 2024Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable...
Moderate intensity aerobic exercise alleviates motor deficits in 6-OHDA lesioned rats and reduces serum levels of biomarkers of Parkinson's disease severity without recovery of striatal dopamine or tyrosine hydroxylase.
Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable by therapeutic approaches. However, evidence for AE-related recovery of striatal dopamine (DA) signaling or tyrosine hydroxylase (TH) loss has been inconsistent in rodent studies. This ambiguity may be related to the timing of AE intervention in relation to the status of nigrostriatal neuron loss. Here, we replicated human PD at diagnosis by establishing motor impairment with >80% striatal DA and TH loss prior to initiating AE, and assessed its potential to alleviate motor decline and restore DA and TH loss. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of human PD severity, changed in response to AE. 6-hydroxydopamine (6-OHDA) was infused unilaterally into rat medial forebrain bundle to induce progressive nigrostriatal neuron loss over 28 days. Moderate intensity AE (3× per week, 40 min/session), began 8-10 days post-lesion following establishment of impaired forelimb use. Striatal tissue DA, TH protein and mRNA, and serum levels of NfL/GFAP were determined 3-wks after AE began. Despite severe striatal DA depletion at AE initiation, forelimb use deficits and hypokinesia onset were alleviated by AE, without recovery of striatal DA or TH protein loss, but reduced NfL and GFAP serum levels. This proof-of-concept study shows AE alleviates motor impairment when initiated with >80% striatal DA loss without obligate recovery of striatal DA or TH protein. Moreover, the AE-related reduction of NfL and GFAP serum levels may serve as objective blood-based biomarkers of AE efficacy.
PubMed: 38944332
DOI: 10.1016/j.expneurol.2024.114875 -
Clinical Neurology and Neurosurgery Jun 2024Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological... (Review)
Review
Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological diseases worldwide. PD is usually diagnosed after the third decade of life with symptoms like tremors at rest and muscle stiffness. Rapid Eye Movement sleep behavioral disorder (RBD) is another disorder that is caused by a loss of typical muscle relaxation during sleep with a lot of motor activity. Usually, RBD is strongly associated with PD. Recent studies have demonstrated that PD reduces the life expectancy of patients to 10 and 20 years after being diagnosed. In addition, delayed diagnosis and treatment of these neurological disorders have significant socio-economic impacts on patients, their partners and on the general public. Often, it is not clear about PD associated financial burdens both in low and high-income countries. On the other hand, PD triggers neurological variations that affect differences in the dopamine transporter (DAT) and in glucose metabolism. Therefore, positron emission tomography (PET) using specific DAT radiotracers and fluorine-18 labeled desoxyglucose (FDG) has being considered a key imaging technique that could be applied clinically for the very early diagnosis of RBD and in PD. However, a few myths about PET is that it is very expensive. Here, we looked at the cost of treatment of PD and RBD in relation to early PET imaging. Our finding suggests that PET imaging might also be a cost sparing diagnostic option in the management of patients with PD and RBD, not only for first world countries as it is the case now but also for the third world countries. Therefore, PET is a cost-effective imaging technique for very early diagnostic of RBD and PD.
PubMed: 38944021
DOI: 10.1016/j.clineuro.2024.108404 -
Clinical Neurophysiology : Official... Jun 2024We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of...
OBJECTIVE
We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry.
METHODS
We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed.
RESULTS
We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12-15 Hz.
CONCLUSIONS
Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both.
SIGNIFICANCE
Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology.
PubMed: 38943791
DOI: 10.1016/j.clinph.2024.06.003