RESUMEN
The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson's disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.
Asunto(s)
Catárticos/farmacología , Dieta , Microbioma Gastrointestinal , Actividad Motora , Enfermedad de Parkinson/microbiología , Enfermedad de Parkinson/fisiopatología , Bacterias/efectos de los fármacos , Estudios de Casos y Controles , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Levodopa/farmacología , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Filogenia , Análisis de Componente PrincipalRESUMEN
Parkinson's disease (PD) is the world's fastest growing neurological disorder disabling patients through a broad range of motor and non-motor symptoms. For the clinical management, a multidisciplinary approach has increasingly been shown to be beneficial. In Germany, inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is a well-established and frequent approach, although data on its effectiveness are rare. We conducted a prospective real-world observational study in 47 subjects [age (M ± SD): 68.5 ± 9.0 years, disease duration: 8.5 ± 5.3 years, modified Hoehn and Yahr stage (median, IQR): 3, 2.5-3] aiming at evaluating the effectiveness of 14-day PD-MCT in terms of quality of life (Parkinson's Disease Questionnaire, EuroQol), motor [Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III], Timed Up and Go Test, Purdue Pegboard Test) and non-motor symptoms (revised Beck Depression Inventory). Six weeks after hospital discharge, a follow-up examination was performed. PD patients with a predominantly moderate disability level benefited from PD-MCT in terms of health-related quality of life, motor symptoms and non-motor symptoms (depression). Significant improvements were found for social support, emotional well-being and bodily discomfort domains of health-related quality of life. Sustainable improvement occurred for motor symptoms and the subjective evaluation of health state. We found a higher probability of motor response especially for patients with moderate motor impairment (MDS-UPDRS III ≥ 33). In conclusion, Parkinson's Disease Multimodal Complex Treatment improves motor symptoms, depression and quality of life. A more detailed selection of patients who will benefit best from this intervention should be examined in future studies.
Asunto(s)
Depresión/rehabilitación , Discinesias/rehabilitación , Rehabilitación Neurológica/métodos , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/rehabilitación , Calidad de Vida , Anciano , Terapia Combinada , Personas con Discapacidad , Discinesias/etiología , Terapia por Ejercicio , Femenino , Estudios de Seguimiento , Humanos , Hipertermia Inducida , Terapia del Lenguaje , Masculino , Masaje , Persona de Mediana Edad , Terapia Ocupacional , Enfermedad de Parkinson/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The aim of the study was to investigate if speciation analysis by liquid chromatography coupled to mass spectrometry could be used to detect organic and inorganic binding forms of selenium in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) and age-matched control subjects (AMC). METHODS: PD patients and control subjects were enrolled from three different neurological departments. CSF samples were collected according to standardized biomarker protocols and subjected to inductively coupled plasma mass spectrometry (ICP-MS) for total selenium determination and ion exchange chromatography (IEC) hyphenated to ICP-MS for selenium speciation analysis. RESULTS: 75 PD patients and 68 age-matched controls were enrolled for speciation analysis. 8 different species could be detected, but only selenoprotein P (SELENOP), human serum albumin-bound Se (Se-HSA), selenomethionine (Se-Met) and an unidentified Se-compound (U2) presented with more than 50% values above the limit of quantification, without showing significant differences between both groups (pâ¯>â¯0.05). The Se-HSA / Se-Met ratio yielded a significant difference between PD and AMC (pâ¯=â¯0.045). The inorganic species Se-IV and Se-VI were only detectable in a minor part of PD and AMC samples. A highly significant correlation between total selenium levels and SELENOP (PD pâ¯<â¯0.0001; AMC pâ¯<â¯0.0001) and Se-HSA (PD pâ¯<â¯0.0001; AMC pâ¯<â¯0.0001) could be demonstrated, respectively. CONCLUSIONS: Speciation analysis yielded new insight into selenium homeostasis in PD but cannot be used to establish a diagnostic biomarker. The small number of detectable values for Se-IV and Se-VI suggests an inferior role of these potentially neurotoxic binding forms in PD pathology in contrast to other neurodegenerative disorders.
Asunto(s)
Enfermedad de Parkinson/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Anciano , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Compuestos de Selenio/líquido cefalorraquídeo , Selenometionina/líquido cefalorraquídeo , Selenoproteína P/líquido cefalorraquídeoRESUMEN
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model. Beginning from day 100, mice were treated with deferiprone (DFP), a ferric chelator that is able to cross the blood-brain barrier and is currently used in clinics as treatment for hemosiderosis. Our paradigm resulted in an impairment of the learning abilities in the rotarod task and the novel object recognition test. DFP treatment significantly improved the performance in both tasks. Although this was not accompanied by alterations in aSyn aggregation, our results support DFP as possible therapeutic option in PD.