RESUMEN
The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system to the pathogenesis of multiple sclerosis (MS). Here, we examined the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also investigated if the treatment with pramipexole (PPX)-a dopamine D2/D3 receptor-preferring agonist-would be able to prevent EAE-induced motor and mood dysfunction, as well as its underlying mechanisms of action. We report that D2R immunocontent is upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontents in lymph nodes and the oxidative damage in the spinal cord and striatum of EAE animals were significantly increased during the chronic phase. Also, during the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. Surprisingly, therapeutic treatment with PPX failed to inhibit the progression of EAE. Of note, PPX treatment inhibited EAE-induced depressive-like while failed to inhibit anhedonic-like behaviors. We observed that PPX treatment downregulated IL-1ß levels and increased BNDF content in the spinal cord after EAE induction. Herein, we show that a D2/D3 receptor-preferred agonist mitigated EAE-induced depressive-like behavior, which could serve as a new possibility for further clinical trials on treating depressive symptoms in MS patients. Thus, we infer that D2R participates in the crosstalk between CNS and immune system during autoimmune and neuroinflammatory response induced by EAE, mainly in the acute and chronic phase of the disease.
Asunto(s)
Encefalomielitis Autoinmune Experimental/metabolismo , Receptores de Dopamina D1/fisiología , Receptores de Dopamina D2/fisiología , Anhedonia/efectos de los fármacos , Anhedonia/fisiología , Animales , Axones/patología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Factor Neurotrófico Derivado del Encéfalo/genética , Cuerpo Estriado/metabolismo , Depresión/etiología , Depresión/prevención & control , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/psicología , Femenino , Interleucina-1beta/biosíntesis , Interleucina-1beta/genética , Ganglios Linfáticos/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Estrés Oxidativo , Fragmentos de Péptidos/biosíntesis , Fragmentos de Péptidos/genética , Pramipexol/farmacología , Pramipexol/uso terapéutico , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistas , Método Simple Ciego , Médula Espinal/metabolismo , Médula Espinal/patologíaRESUMEN
The aim of this study was to develop biodegradable films using fruit and vegetable residue (FVR) flour with different granulometry range and pectin levels. The FVR flour was divided in three fractions, according to their granulometric distribution: A (425-500⯵m), B (212-300⯵m) and C (<150⯵m). FVR presented heterogeneous particle size distribution and fibrous structure showing granular compounds adhered to the surface. The fiber contents decreased according to granulometry, whereas the protein content increased. The films obtained from FVR were malleable, homogeneous, yellowish, and presented high solubility (90%). The granulometry reduction and the pectin addition have significantly improved the viscosity and the yellow color of the film solutions (FS). There was decrease of solubility (50%) and improvement of the mechanical properties of the pectin-based films: decrease of elongation (16-30%) and increase of tensile strength (2.88⯱â¯0.79â¯MPa). The sorption isotherms of the pectin-FVR films evidenced the lower availability of polar groups able to work as water-sorption sites. Therefore, different residue fractions could have different applications depending on their particle size and composition, either as source of dietary fibers (the thickest fractions) or as raw material for film production.
Asunto(s)
Plásticos Biodegradables/química , Harina/análisis , Frutas , Pectinas/química , Verduras , Fenómenos Químicos , Colorimetría , Fibras de la Dieta/análisis , Embalaje de Alimentos , Lípidos/análisis , Fenómenos Mecánicos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Proteínas de Vegetales Comestibles/análisis , Reología , Almidón/química , Azúcares/análisis , Resistencia a la Tracción , Agua/químicaRESUMEN
Agro-industrial byproducts are considered good sources of macronutrients and phytochemicals. Fruit and vegetable residues (FVR), obtained after the production of an isotonic beverage, have previously been characterized containing 80% insoluble dietary fibers from total fibers (48.4%), 26% available carbohydrates, 9.5% proteins and 5% lipids. Nevertheless, fruit and vegetables provide phytochemicals which have been related to human health such as phenolic compounds. The loss of specific compounds over the production process is related to their partitioning between fruit and vegetables and byproducts. However, phenolic profile of FVR remains unknown. This work is focused on the evaluation of FVR as a natural source of these bioactive compounds. For this purpose, pressurized liquid extraction (PLE) has been proposed as extraction technique for recovering phenolic compounds from FVR. The experimental variables were temperature and percentage of solvent (ethanol and water). Phenolic compounds extracts were characterized by UPLC-ESI-Q-TOF-MS and a discussion about phenolic and macronutrient interactions was established. Globally, 88 compounds were tentatively identified: phenolic acids (28), flavonoids (32), and other polyphenols (28). The PLE conditions applied yielded different breaking matrix-analyte interactions leading to an increase in the number of compounds. The highest phenolic acids content was achieved with high temperature while lower temperatures were more efficient in extracting flavonoid. By establishing the phenolics profile in food byproducts such as FVR, it is possible to more effectively apply these byproducts as nutraceutical, food or pharmaceutical ingredients. PRACTICAL APPLICATION: Flow diagram of bioactive compounds recovering from isotonic beverage byproduct is proposed using pressurized liquid extraction. The plant-bioactives mechanism relies on fruit and vegetable byproducts changes under different extraction conditions. The obtained extracts can most effectively be applied as nutraceuticals or as ingredients in food or pharmaceutical inputs.
Asunto(s)
Bebidas/análisis , Fraccionamiento Químico/métodos , Frutas/química , Nutrientes/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Verduras/química , Residuos/análisis , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Fraccionamiento Químico/instrumentación , Fibras de la Dieta/análisis , Manipulación de Alimentos , Nutrientes/química , Fitoquímicos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polifenoles/química , Polifenoles/aislamiento & purificaciónRESUMEN
Proteomic profiles of the thalamus and the correlation between the rats' performance on a spatial learning task and differential protein expression were assessed in the thiamine deficiency (TD) rat model of Wernicke-Korsakoff syndrome. Two-dimensional gel-electrophoresis detected 320 spots and a significant increase or decrease in seven proteins. Four proteins were correlated to rat behavioral performance in the Morris Water Maze. One of the four proteins was identified by mass spectrometry as Voltage-Dependent Anion Channels (VDACs). The association of VDAC is evident in trials in which the rats' performance was worst, in which the VDAC protein was reduced, as confirmed by Western blot. No difference was observed on the mRNA of Vdac genes, indicating that the decreased VDAC expression may be related to a post-transcriptional process. The results show that TD neurodegeneration involves changes in thalamic proteins and suggest that VDAC protein activity might play an important role in an initial stage of the spatial learning process.