RESUMEN
Recent research has focused on the link between diet, intestinal microbiota, and the impact of excessive consumption of saturated fatty acids. Saturated fatty acids, found in animal fats, dairy, and processed foods, contribute to dysbiosis, increase intestinal barrier permeability, chronic low-grade inflammation, oxidative stress, and dysfunction of the blood-brain barrier, affecting the central nervous system. High intake of saturated fatty acids is associated with an increased risk of developing Parkinson's disease (PD). Diets low in saturated fats, rich in fibers, promote microbial diversity, improve gut health, and potentially reduce the risk of neurodegenerative diseases like PD.
Asunto(s)
Microbioma Gastrointestinal , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Enfermedad de Parkinson/etiología , Microbioma Gastrointestinal/fisiología , Inflamación , Dieta , Ácidos GrasosRESUMEN
Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.
Asunto(s)
Enfermedad de Parkinson , Ratas , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Simvastatina/farmacología , Simvastatina/uso terapéutico , Simvastatina/metabolismo , Proteómica , Sustancia Negra/metabolismo , Dopamina/metabolismo , 1-Metil-4-fenilpiridinio/farmacología , Cuerpo Estriado/metabolismo , Modelos Animales de EnfermedadRESUMEN
The prevalence of Parkinson's disease (PD) is growing worldwide and household pesticides exposure may be related to this phenomenon. We showed that individuals with high exposure to household pesticides have two times more risk of developing PD. Household pesticide exposure did not impact age at PD onset.
Asunto(s)
Enfermedad de Parkinson , Plaguicidas , Humanos , Plaguicidas/toxicidad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Brasil/epidemiología , Factores de Riesgo , Prevalencia , Exposición a Riesgos AmbientalesRESUMEN
It is well-known that consumption of synthetic and natural food additives has both positive and negative effects in the human body. However, it is not clear yet how food additives are related to the development of Parkinson's disease. Therefore, in this review work, the food additive effects related to the gut microbiota-brain axis and the processes that are carried out to develop Parkinson's disease are studied. To this end, a systematic literature analysis is performed with the selected keywords and the food additive effects are studied to draw possible routes of action. This analysis leads to the proposition of a model that explains the pathways that relate the ingestion of food additives to the development of Parkinson's disease. This work motivates further research that ponders the safety of food additives by measuring their impacts over the gut microbiota-brain axis.
Asunto(s)
Microbioma Gastrointestinal , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Aditivos Alimentarios/efectos adversos , Aditivos Alimentarios/metabolismo , Encéfalo/metabolismo , Transducción de SeñalRESUMEN
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that results in a decrease in dopamine levels, resulting in motor-type disturbances. Different vertebrate models, such as rodents and fish, have been used to study PD. In recent decades, Danio rerio (zebrafish) has emerged as a potential model for the investigation of neurodegenerative diseases due to its homology to the nervous system of humans. In this context, this systematic review aimed to identify publications that reported the utilization of neurotoxins as an experimental model of parkinsonism in zebrafish embryos and larvae. Ultimately, 56 articles were identified by searching three databases (PubMed, Web of Science, and Google Scholar). Seventeen studies using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 4 1-methyl-4-phenylpyridinium (MPP+), 24 6-hydroxydopamine (6-OHDA), 6 paraquat/diquat, 2 rotenone, and 6 articles using other types of unusual neurotoxins to induce PD were selected. Neurobehavioral function, such as motor activity, dopaminergic neuron markers, oxidative stress biomarkers, and other relevant parameters in the zebrafish embryo-larval model were examined. In summary, this review provides information to help researchers determine which chemical model is suitable to study experimental parkinsonism, according to the effects induced by neurotoxins in zebrafish embryos and larvae.
Asunto(s)
Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Trastornos Parkinsonianos , Humanos , Animales , Neurotoxinas/efectos adversos , Pez Cebra , Enfermedad de Parkinson/etiología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Larva , Trastornos Parkinsonianos/inducido químicamente , Modelos Teóricos , Modelos Animales de EnfermedadRESUMEN
Parkinson's disease (PD) is an incurable neurodegenerative disease of high prevalence, characterized by the prominent death of dopaminergic neurons in the substantia nigra pars compacta, which produces dopamine deficiency, leading to classic motor symptoms. Although PD has traditionally been considered as a neuronal cell autonomous pathology, in which the damage of vulnerable neurons is responsible for the disease, growing evidence strongly suggests that astrocytes might have an active role in the neurodegeneration observed. In the present review, we discuss several studies evidencing astrocyte implications in PD, highlighting the consequences of both the loss of normal homeostatic functions and the gain in toxic functions for the wellbeing of dopaminergic neurons. The revised information provides significant evidence that allows astrocytes to be positioned as crucial players in PD etiology, a factor that needs to be taken into account when considering therapeutic targets for the treatment of the disease.
Asunto(s)
Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/patología , Astrocitos/patología , Sustancia Negra/patología , Enfermedades Neurodegenerativas/patología , Neuronas Dopaminérgicas/patologíaRESUMEN
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.
Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Animales , Ratas , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Oxidopamina , Inflamasomas/metabolismo , Electrodos , Glutamatos , Inflamación/terapia , Citocinas/metabolismo , Sistemas de Transporte de Aminoácidos , Ácido gamma-AminobutíricoRESUMEN
Parkinson's disease (PD) is characterized by four pathognomonic hallmarks: (1) motor and non-motor deficits; (2) neuroinflammation and oxidative stress; (3) pathological aggregates of the α-synuclein (α-syn) protein; (4) neurodegeneration of the nigrostriatal system. Recent evidence sustains that the aggregation of pathological α-syn occurs in the early stages of the disease, becoming the first trigger of neuroinflammation and subsequent neurodegeneration. Thus, a therapeutic line aims at striking back α-synucleinopathy and neuroinflammation to impede neurodegeneration. Another therapeutic line is restoring the compromised dopaminergic system using neurotrophic factors, particularly the glial cell-derived neurotrophic factor (GDNF). Preclinical studies with GDNF have provided encouraging results but often lack evaluation of anti-α-syn and anti-inflammatory effects. In contrast, clinical trials have yielded imprecise results and have reported the emergence of severe side effects. Here, we analyze the discrepancy between preclinical and clinical outcomes, review the mechanisms of the aggregation of pathological α-syn, including neuroinflammation, and evaluate the neurorestorative properties of GDNF, emphasizing its anti-α-syn and anti-inflammatory effects in preclinical and clinical trials.
Asunto(s)
Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Enfermedad de Parkinson/metabolismo , Agregación Patológica de Proteínas , alfa-Sinucleína/metabolismo , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Humanos , Enfermedades Neuroinflamatorias/etiología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiologíaRESUMEN
Parkinson's disease (PD) is a chronic neurodegenerative disorder mainly attributed to the progressive loss of dopaminergic neurons in the substantia nigra, which leads to uncontrolled voluntary movements causing tremors, postural instability, joint stiffness, and speech and locomotion difficulties, among other symptoms. Previous studies have shown the participation of specific peptides in neurodegenerative diseases. In this context, the present work analyzed changes in the peptide profile in zebrafish brain induced to parkinsonian conditions with 6-hydroxydopamine, using isotopic labeling techniques plus mass spectrometry. These analyses allowed the relative quantitation and identification of 118 peptides. Of these, nine peptides showed significant changes, one peptide was increased and eight decreased. The most altered sequences were fragment of cytosolic and extracellular proteins related to lipid metabolism and dynamic cytoskeleton. These results open new perspectives of study about the function of peptides in PD.
Asunto(s)
Encéfalo/metabolismo , Oxidopamina/farmacología , Enfermedad de Parkinson/metabolismo , Péptidos/metabolismo , Pez Cebra/metabolismo , Animales , Enfermedad de Parkinson/etiologíaRESUMEN
Chronic consumption of ß-sitosterol-ß-D-glucoside (BSSG), a neurotoxin contained in cycad seeds, leads to Parkinson's disease in humans and rodents. Here, we explored whether a single intranigral administration of BSSG triggers neuroinflammation and neurotoxic A1 reactive astrocytes besides dopaminergic neurodegeneration. We injected 6 µg BSSG/1 µL DMSO or vehicle into the left substantia nigra and immunostained with antibodies against tyrosine hydroxylase (TH) together with markers of microglia (OX42), astrocytes (GFAP, S100ß, C3), and leukocytes (CD45). We also measured nitric oxide (NO), lipid peroxidation (LPX), and proinflammatory cytokines (TNF-α, IL-1ß, IL-6). The Evans blue assay was used to explore the blood-brain barrier (BBB) permeability. We found that BSSG activates NO production on days 15 and 30 and LPX on day 120. Throughout the study, high levels of TNF-α were present in BSSG-treated animals, whereas IL-1ß was induced until day 60 and IL-6 until day 30. Immunoreactivity of activated microglia (899.0 ± 80.20%) and reactive astrocytes (651.50 ± 11.28%) progressively increased until day 30 and then decreased to remain 251.2 ± 48.8% (microglia) and 91.02 ± 39.8 (astrocytes) higher over controls on day 120. C3(+) cells were also GFAP and S100ß immunoreactive, showing they were neurotoxic A1 reactive astrocytes. BBB remained permeable until day 15 when immune cell infiltration was maximum. TH immunoreactivity progressively declined, reaching 83.6 ± 1.8% reduction on day 120. Our data show that BSSG acute administration causes chronic neuroinflammation mediated by activated microglia, neurotoxic A1 reactive astrocytes, and infiltrated immune cells. The severe neuroinflammation might trigger Parkinson's disease in BSSG intoxication.
Asunto(s)
Astrocitos/efectos de los fármacos , Astrocitos/inmunología , Inflamación/etiología , Neurotoxinas/inmunología , Sitoesteroles/administración & dosificación , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , Animales , Astrocitos/metabolismo , Biomarcadores , Enfermedad Crónica , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Microglía/inmunología , Microglía/metabolismo , Neurotoxinas/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Ratas , Sustancia Negra/patologíaRESUMEN
OBJECTIVE: To evaluate the relationship between occupational and environmental exposure to pesticides and Parkinson disease in a region of intense agribusiness activity in the state of Mato Grosso/Brazil. METHODS: Case-control study carried out in a referral hospital for chronic neurodegenerative diseases. Non-conditional logistic regression analyses were performed. RESULTS: Having performed direct management of pesticides in the workplace (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.55 to 7.28), having a family history of Parkinson (OR: 3.42; 95% CI: 1.61 to 7.28) and being men (OR: 3.01; 95% CI: 1.66 to 5.45) were all factors that contributed to a greater chance for the development of the disease. CONCLUSION: Our study reinforces the associations between occupational and environmental exposure to pesticides and the occurrence of Parkinson disease in regions of intense agribusiness activity in Brazil.
Asunto(s)
Exposición Profesional , Enfermedad de Parkinson , Plaguicidas , Brasil/epidemiología , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Masculino , Exposición Profesional/efectos adversos , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Plaguicidas/toxicidad , Factores de RiesgoAsunto(s)
COVID-19/complicaciones , Disbiosis/complicaciones , Microbioma Gastrointestinal , Enfermedad de Parkinson/etiología , SARS-CoV-2/patogenicidad , Traslocación Bacteriana/inmunología , COVID-19/microbiología , Sistema Nervioso Entérico/fisiopatología , Humanos , Inflamación , Lipopolisacáridos/metabolismo , Lipopolisacáridos/toxicidad , Microglía/inmunología , Microglía/metabolismo , Modelos Biológicos , Neuroinmunomodulación , Enfermedad de Parkinson/microbiología , Agregación Patológica de Proteínas , Factores de Riesgo , Nervio Vago/fisiopatología , alfa-Sinucleína/metabolismoRESUMEN
Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1ß, cleaved IL-1ß, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1ß, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1ß in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1ß and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.
Asunto(s)
Ácidos Anacárdicos/farmacología , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Plaguicidas/toxicidad , Ácidos Anacárdicos/química , Ácidos Anacárdicos/aislamiento & purificación , Animales , Simulación por Computador , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Proteína Ácida Fibrilar de la Glía/genética , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Humanos , Interleucina-1beta/genética , Peroxidación de Lípido/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/genética , Ratones , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/patología , Inhibidor Tisular de Metaloproteinasa-1/genética , Factor de Transcripción ReIA/genética , Tirosina 3-Monooxigenasa/genéticaRESUMEN
The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/crecimiento & desarrollo , Enfermedad de Parkinson/etiología , Fenoles/toxicidad , Animales , Catalasa/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Femenino , Glutatión Transferasa/metabolismo , Humanos , Masculino , Malondialdehído/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Nivel sin Efectos Adversos Observados , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: A link between diabetes and Parkinson´s disease (PD) has been established by several reports. Consistent data report that people diagnosed with diabetes have demonstrated an enhanced risk of manifesting PD in their lifetime. The working principles involved in this link have been extensively discussed. Over the last decade, diabetes has been reported to be correlated with an increased risk of dementia, suggesting a potential role of diabetes, or insulin signalling dysregulations, in neurodegeneration. In addition, it is nowadays highly debated that dysregulations related to Ca2+ signalling may be an upstream issue which could also link diabetes and PD. Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control both the neurotransmitters/hormones release and neuronal death. CONCLUSION: Considering our previous reports about Ca2+/cAMP signalling, the putative contribution of Ca2+/cAMP signalling in this link (between diabetes and PD) is discussed in this paper.
Asunto(s)
Calcio/fisiología , AMP Cíclico/fisiología , Diabetes Mellitus/fisiopatología , Enfermedad de Parkinson/fisiopatología , Transducción de Señal/fisiología , Humanos , Enfermedad de Parkinson/etiologíaRESUMEN
This investigation aimed to conduct a systematic review of the literature and meta-analysis to determine whether exposure to the herbicide paraquat was associated with the development of Parkinson's disease (PD). Observational studies that enrolled adults exposed to paraquat with PD as the outcome of interest were searched in the PubMed, Embase, LILACS, TOXNET, and Web of Science databases up to May 2019. Two authors independently selected relevant studies, extracted data, and assessed methodological quality. The evidence certainty was assessed by the GRADE approach, which served as basis for a tentative causality assessment, supplemented by the Bradford Hill criteria when necessary. Results from nine case-control studies indicated that PD occurrence was 25% higher in participants exposed to paraquat. The only cohort investigation included demonstrated a non-significant OR of 1.08. Results from subgroup analyses also indicated higher PD frequency in participants that were exposed to paraquat for longer periods or individuals co-exposed with paraquat and any other dithiocarbamate. Data indicate apositive association between exposure to paraquat and PD occurrence, but the weight-of-evidence does not enable one to assume an indisputable cause-effect relationship between these two conditions. Better designed studies are needed to increase confidence in results. Systematic Review Registration: PROSPERO CRD42017069994.
Asunto(s)
Herbicidas/toxicidad , Paraquat/toxicidad , Enfermedad de Parkinson/etiología , Adulto , Humanos , Enfermedad de Parkinson/epidemiología , Proyectos de Investigación , Factores de TiempoRESUMEN
In the 90's, clinico pathological studies have considerably improved the diagnosis of specific and rare neurodegenerative diseases. After a training in Parkinsons' disease in Paris, the author moved to French West Indies (Guadeloupe) and observed a high incidence of atypical parkinsonism with dementia, unresponsive to levodopa. Similar features were observed in Martinique. An environmental origin has been suspected with the exposure to toxins of annonaceae leaves and seeds. The candidate toxins are acetogenins acting as mitochondrial poison. This was demonstrated in neuronal cell cultures, and in animals. However, the agency for food security did not conclude that Annonaceae should not be used for herbal (medicinal) tea, even if the population is now aware about the possible risk of parkinsonism after exposure to annonaceae acetogenins.
Asunto(s)
Annonaceae/química , Demencia , Alimentos/toxicidad , Trastornos Parkinsonianos , Tés de Hierbas/toxicidad , Región del Caribe/epidemiología , Demencia/complicaciones , Demencia/epidemiología , Demencia/etiología , Resistencia a Medicamentos , Guadalupe/epidemiología , Humanos , Levodopa/uso terapéutico , Martinica/epidemiología , Enfermedad de Parkinson/clasificación , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/epidemiología , Trastornos Parkinsonianos/etiología , Indias Occidentales/epidemiologíaRESUMEN
BACKGROUND: There is some evidence to suggest an association between ambient air pollution and development of Parkinson's disease (PD). However, the small number of studies published to date has reported inconsistent findings. OBJECTIVES: To assess the association between long-term exposure to ambient air pollution constituents and the development of PD. METHODS: Air pollution exposures (particulate matter with aerodynamic diameter <10⯵m [PM10], <2.5⯵m [PM2.5], between 2.5⯵m and 10⯵m [PMcoarse], black carbon, and nitrogen oxides [NO2 and NOx]) were predicted based on land-use regression models developed within the "European Study for Air Pollution Effects" (ESCAPE) study, for a Dutch PD case-control study. A total of 1290 subjects (436 cases and 854 controls). were included and 16â¯years of exposure were estimated (average participant starting age: 53). Exposures were categorized and conditional logistic regression models were applied to evaluate the association between ambient air pollution and PD. RESULTS: Overall, no significant, positive relationship between ambient air pollutants and PD was observed. The odds ratio (OR) for PD associated with an increase from the first quartile of NO2 (<22.8⯵g/m3) and the fourth (>30.4⯵g/m3) was 0.87 (95% CI: 0.54, 1.41). For PM2.5 where the contrast in exposure was more limited, the OR associated with an increase from the first quartile PM2.5 (<21.2⯵g/m3) to the fourth (>22.3⯵g/m3) was 0.50 (95% CI: 0.24, 1.01). In a subset of the population with long-term residential stability (nâ¯=â¯632), an increased risk of PD was observed (e.g. OR for Q4 vs Q1 NO2:1.37, 95% CI: 0.71, 2.67). CONCLUSIONS: We found no clear association between 16â¯years of residential exposure to ambient air pollution and the development of PD in The Netherlands.
Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales/análisis , Enfermedad de Parkinson/epidemiología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Óxidos de Nitrógeno/análisis , Enfermedad de Parkinson/etiología , Material Particulado/análisis , Hollín/análisisRESUMEN
Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.