RESUMEN
In humans, the pituitary gland is covered by a fibrous capsule and is considered a continuation of the meningeal sheath. However, in rodents some studies concluded that only the pars tuberalis (PT) and pars nervosa (PN) are enwrapped by the pia mater, while others showed that the whole gland is covered by this sheath. At PT the median eminence subarachnoid drains cerebrospinal fluid (CSF) to its cisternal system representing a pathway to the hypothalamus. In the present study we examined the rat pituitary capsule to elucidate its configuration, its physical interaction with the pituitary border and its relationship with the CSF. Furthermore, we also revisited the histology of the pituitary cleft and looked whether CSF drained in it. To answer such questions, we used scanning and transmission electron microscopy, intracerebroventricular infusion of Evan´s blue, fluorescent beads, and sodium fluorescein. The latter was measured in the pars distalis (PD) and various intracranial tissues. We found a pituitary capsule resembling leptomeninges, thick at the dorsal side of the pars intermedia (PI) and PD, thicker at the level of PI in contiguity with the PN and thinner at the rostro-ventral side as a thin membrane of fibroblast-like cells embedded in a fibrous layer. The capsule has abundant capillaries on all sides. Our results showed that the CSFs bathe between the capsule and the surface of the whole gland, and ciliate cells are present in the pituitary border. Our data suggest that the pituitary gland intercommunicates with the central nervous system (CNS) through the CSF.
Asunto(s)
Adenohipófisis , Hipófisis , Humanos , Ratas , Animales , Hipófisis/metabolismo , Hipotálamo , Adenohipófisis/metabolismoRESUMEN
We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Sprague Dawley rats (SD). At embryonic day 15 (E15), healthy pregnant SD rats were given taurine treatment (50 mg/L drinking water) and then to their male offspring until they reached the age of eight months. We quantify, in the offspring, the concentration of nitric oxide (NO) through the Griess colorimetric reaction [1] and malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) by the Gérard-Monnier technique [2]. The assessment ages for NO and MDA + 4-HDA were at postnatal day 15 (PND15), 1, 3, and 8 months of age. The body weight was measured along with the integral motor behavior in the perinatal stage through the surface righting reflex test at PND5, cliff aversion test at PND9, grip strength test at PND 11, and front limb and hindlimb suspension tests at PND13. The tests were performed accordingly with [3]. The data obtained showed that SD rats with the taurine administration performed poorly in the motor tests compared with the untreated healthy rats. The taurine-treated rats also showed increased lipid peroxidation preferentially in cerebral regions involved in motor activity, such as the medulla oblongata, the subcortical nuclei, and the cerebral cortex. However, the taurine treatment only increased NO concentration in the evaluated cerebral regions at older ages. At E15, taurine plays a pivotal role in the excitatory/inhibitory neuromodulation, presumably by acting as an excitatory neurotransmitter during the GABA-switch [4]. The increase in the taurine concentration during the embryonic period might cause excitotoxicity in healthy brains, which might lead to impairments in the motor development of the offspring. Therefore, the present datasets can be valuable for researchers who attempt to use the taurine supplement on healthy animal models at gestational stages; and explore the relation with taurine intake during pregnancy in human patients. These datasets are related to the article "Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative stress and promoting myelination" [5].
RESUMEN
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
BackgroundDasapatrachurnam (DPC), a multicurative powder prepared from the leaves of 10 green leafy vegetables, was developed recently with known ethnobotanical and ethnopharmacological significance. However, its functional role in curing a disease is not yet scientifically proven. The present study aims at performing the phytochemical screening of DPC and exploring its possible activity as bacteriostatic, antineoplastic and anti-inflammatory. MethodsWe performed qualitative and Fourier transform infrared spectroscopy (FTIR) to find out the presence of active compounds and tested the bacteriostatic activity in four bacterial strains namely Bacillus subtilis, Escherichia coli, Streptococcus pyogenes and Staphylococcus aureus by agar well diffusion method. We further explored the antineoplastic activity in vitro in C6 and HEK293 cell lines by cell viability assay and the anti-inflammatory activity in the ovalbumin-induced inflammation in male Wistar rats. ResultsDPC showed 60% solubility in PBS and showed the presence of flavonoids and glycosides. FTIR results indicated the presence of alkyl, ketone and aldehyde groups. The bacteriostatic activity of DPC was higher (60%) in E.coli and lower (8%) in S.aureus, when compared to streptomycin. The anti-cancerous activity of DPC in C6 and HEK293 cancer cells was similar to their respective positive controls, curcumin and camptothecin. The anti-inflammatory activity of DPC was more evident with local administration in all the parameters studied in brain hippocampus, kidney, liver and spleen in ovalbumin-induced rats. ConclusionOur results, for the first time, suggest the potentiality of the DPC in treating bacterial diseases, cancer and also inflammation. Our results also suggest the possible therapeutic role of DPC in treating chronic kidney disease.
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Suplementos Dietéticos/análisis , Fitoquímicos/farmacología , Hojas de la Planta/química , Preparaciones de Plantas/farmacología , Verduras/química , Animales , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Bacterias/efectos de los fármacos , Flavonoides/análisis , Glicósidos/análisis , Células HEK293 , Humanos , Masculino , Polvos , Ratas , Ratas WistarRESUMEN
In the cerebral hypoxia-ischemia rat model, the prophylactic administration of zinc can cause either cytotoxicity or preconditioning effect, whereas the therapeutic administration of selenium decreases the ischemic damage. Herein, we aimed to explore whether supplementation of low doses of prophylactic zinc and therapeutic selenium could protect from a transient hypoxic-ischemic event. We administrated zinc (0.2 mg/kg of body weight; ip) daily for 14 days before a 10 min common carotid artery occlusion (CCAO). After CCAO, we administrated sodium selenite (6 µg/kg of body weight; ip) daily for 7 days. In the temporoparietal cerebral cortex, we determined nitrites by the Griess method and lipid peroxidation by the Gerard-Monnier assay. qPCR was used to measure mRNA of nitric oxide synthases, antioxidant enzymes, chemokines, and their receptors. We measured the enzymatic activity of SOD and GPx and protein levels of chemokines and their receptors by ELISA. We evaluated long-term memory using the Morris-Water maze test. Our results showed that prophylactic administration of zinc caused a preconditioning effect, decreasing nitrosative/oxidative stress and increasing GPx and SOD expression and activity, as well as eNOS expression. The therapeutic administration of selenium maintained this preconditioning effect up to the late phase of hypoxia-ischemia. Ccl2, Ccr2, Cxcl12, and Cxcr4 were upregulated, and long-term memory was improved. Pyknotic cells were decreased suggesting prevention of neuronal cell death. Our results show that the prophylactic zinc and therapeutic selenium administration induces effective neuroprotection in the early and late phases after CCAO.
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Antioxidantes/metabolismo , Corteza Cerebral/efectos de los fármacos , Hipoxia-Isquemia Encefálica/metabolismo , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Selenito de Sodio/administración & dosificación , Zinc/administración & dosificación , Animales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
BACKGROUND: Oleosin is a plant protein localized to lipid droplets and endoplasmic reticulum of plant cells. Our idea was to use it to target functional secretory proteins of interest to the cytosolic side of the endoplasmic reticulum of mammalian cells, through expressing oleosin-containing chimeras. We have designed this approach to create cellular models deficient in vitamin B12 (cobalamin) because of the known problematics associated to the obtainment of effective vitamin B12 deficient cell models. This was achieved by the overexpression of transcobalamin inside cells through anchoring to oleosin. METHODOLOGY: chimera gene constructs including transcobalamin-oleosin (TC-O), green fluorescent protein-transcobalamin-oleosin (GFP-TC-O) and oleosin-transcobalamin (O-TC) were inserted into pAcSG2 and pCDNA3 vectors for expression in sf9 insect cells, Caco2 (colon carcinoma), NIE-115 (mouse neuroblastoma), HEK (human embryonic kidney), COS-7 (Green Monkey SV40-transfected kidney fibroblasts) and CHO (Chinese hamster ovary cells). The subcellular localization, the changes in vitamin B12 binding activity and the metabolic consequences were investigated in both Caco2 and NIE-115 cells. PRINCIPAL FINDINGS: vitamin B12 binding was dramatically higher in TC-O than that in O-TC and wild type (WT). The expression of GFP-TC-O was observed in all cell lines and found to be co-localized with an ER-targeted red fluorescent protein and calreticulin of the endoplasmic reticulum in Caco2 and COS-7 cells. The overexpression of TC-O led to B12 deficiency, evidenced by impaired conversion of cyano-cobalamin to ado-cobalamin and methyl-cobalamin, decreased methionine synthase activity and reduced S-adenosyl methionine to S-adenosyl homocysteine ratio, as well as increases in homocysteine and methylmalonic acid concentration. CONCLUSIONS/SIGNIFICANCE: the heterologous expression of TC-O in mammalian cells can be used as an effective strategy for investigating the cellular consequences of vitamin B12 deficiency. More generally, expression of oleosin-anchored proteins could be an interesting tool in cell engineering for studying proteins of pharmacological interest.
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Retículo Endoplásmico/metabolismo , Proteínas de Plantas/metabolismo , Transcobalaminas/metabolismo , Vitamina B 12/metabolismo , Animales , Secuencia de Bases , Western Blotting , Línea Celular , Cartilla de ADN , ADN Complementario , Electroforesis en Gel de Poliacrilamida , Humanos , Microscopía ConfocalRESUMEN
BACKGROUND: We recently reported that (Lamiaceae) may alleviate CCl(4)-induced acute hepatotoxicity in rats, possibly blocking the formation of free radicals generated during CCl(4) metabolism. Carnosol, one of the main constituents of Rosmarinus, has been shown to have antioxidant and scavenging activities. Therefore, it is plausible to expect that carnosol may mediate some of the effects of Rosmarinus on oxidative stress consequences induced by CCl(4) in the liver. DESIGN: We evaluated the effectiveness of carnosol to normalize biochemical and histological parameters of CCl(4)-induced acute liver injury. METHODS: Male Sprague Dawley rats (n = 5) injured by CCl(4) (oral dose 4 g/kg of body weight) were treated with a single intraperitoneal dose (5 mg/kg) of carnosol. Twenty-four hours later, the rats were anaesthetized deeply to obtain the liver and blood, and biochemical and histological parameters of liver injury were evaluated. RESULTS: Carnosol normalized bilirubin plasma levels, reduced malondialdehyde (MDA) content in the liver by 69%, reduced alanine aminotransferase (ALT) activity in plasma by 50%, and partially prevented the fall of liver glycogen content and distortion of the liver parenchyma. CONCLUSIONS: Carnosol prevents acute liver damage, possibly by improving the structural integrity of the hepatocytes. To achieve this, carnosol could scavenge free radicals induced by CCl(4), consequently avoiding the propagation of lipid peroxides. It is suggested that at least some of the beneficial properties of Rosmarinus officinalis are due to carnosol.