Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3ß survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3ß pathway's activation by decreasing the phosphorylation levels of Akt and GSK3ß and Bcl2 levels, which were ameliorated by CBD. The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3ß survival pathway's activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.
Behavior, Animal/drug effects , Cannabidiol/pharmacology , Estrogens/deficiency , Glycogen Synthase Kinase 3 beta/drug effects , Memory Disorders/drug therapy , Proto-Oncogene Proteins c-akt/drug effects , Animals , Brain/metabolism , Female , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus/metabolism , Models, Theoretical , Ovariectomy , Proto-Oncogene Proteins c-akt/metabolism , Rats , Signal Transduction
Estrogens, particularly 17ß-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERß, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.
Memory/physiology , Receptors, G-Protein-Coupled/physiology , Recognition, Psychology/physiology , Animals , Avoidance Learning/drug effects , Avoidance Learning/physiology , Estrogen Receptor Antagonists/pharmacology , Estrogens/pharmacology , Male , Memory/drug effects , Motivation/physiology , Rats , Rats, Wistar , Receptors, G-Protein-Coupled/drug effects , Recognition, Psychology/drug effects
Iron accumulation in the brain has been associated with neurodegenerative disorders, and imaging studies in humans indicate that iron content in brain regions correlates with poor performance in cognitive tasks. In rats, iron overload impairs memory retention in a variety of memory tasks. Although the effects of iron on cognition in rodents are extensively reported, no previous study has been conducted in female rats. The incidence of certain dementias, such as Alzheimer's disease, is higher in women after menopause compared to aged-matched men. The role of oestrogen depletion in memory deficits in menopausal women is still a matter of debate. The present study aimed to characterise the effects of iron overload on memory in female rats by investigating the effects of ovariectomy (OVX, an experimental model of oestrogen depletion) in rats submitted to iron overload, as well as examining the effects of G protein-coupled oestrogen receptor (GPER) agonism on memory impairments induced by iron and OVX. Female rats received iron (30 mg kg-1 , orally) or vehicle at postnatal days 12-14 and were submitted to OVX in adulthood. Results showed that either iron or OVX impaired memory for object placement and inhibitory avoidance. The selective GPER agonist G1, administered immediately after training, reversed both iron- and OVX-induced memory impairments. G1 effects were abolished by protein kinase A (PKA) inhibition, suggesting the involvement of the cAMP/PKA/CREB signalling pathway. The search for novel oestrogen agonists with positive effects on cognition may be promising for the development of treatments for memory disorders.
Iron/adverse effects , Isoquinolines/pharmacology , Memory Disorders/physiopathology , Ovariectomy/psychology , Receptors, Estrogen/physiology , Signal Transduction/physiology , Sulfonamides/pharmacology , Animals , Cyclic AMP/physiology , Cyclic AMP Response Element-Binding Protein/physiology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/physiology , Estrogens/pharmacology , Female , Male , Memory Disorders/chemically induced , Rats , Receptors, Estrogen/drug effects
Aging is associated with a progressive decline in physical and neurophysiological functions, and some studies suggest that cerebral serotonin is decreased in older adults. These factors contribute to reduced ability to perform daily activities, influencing quality of life (QoL). Regular physical activity has demonstrated important benefits in reversing ageing effects; however, little is known whether different training protocols might induce differential effects on QoL. The aim of this study was to verify the effects of different types of training on QoL and its relation with plasma serotonin in healthy older women. Forty-eight older women were randomly assigned in four groups: Strength Training (ST), Endurance Training (ET), Combined Training (CT), and Control Group (CG) which was instructed not to engage in any physical exercise during the study time. Participants underwent 12 weeks of training twice a week. Plasma serotonin and a scoring system questionnaire SF-36 for evaluation of QoL were assessed at baseline and after the completion of training protocols. When comparing pre- and post-training periods all trained groups showed improvement in QoL, but the CT improved more domains. Plasma serotonin was significantly lower in the ST and in the CT groups in comparison with controls after the 12-week training. Significant correlations of plasma serotonin with physical functioning, role-physical, general health, vitality, and mental health were observed. CT resulted in higher amelioration in QoL, in comparison with ET or ST only. All training protocols induced significant reductions in peripheral serotonin levels, which were negatively correlated with improvements in QoL.
Aging , Endurance Training/methods , Quality of Life , Resistance Training/methods , Serotonin/blood , Aged , Aging/physiology , Aging/psychology , Case-Control Studies , Female , Humans , Random Allocation , Surveys and Questionnaires
Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson's disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75NTR, catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1.
Antioxidants/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Deferiprone/pharmacology , Disease Models, Animal , Iron Chelating Agents/pharmacology , Memory Disorders/drug therapy , Oxidative Stress/drug effects , Animals , Antioxidants/chemistry , Brain-Derived Neurotrophic Factor/analysis , Deferiprone/chemistry , Female , Hippocampus/drug effects , Iron Chelating Agents/chemistry , Rats , Rats, Wistar
A dispneia aguda é uma intercorrência comum nos pacientes hospitalizados. Diversas são as condições clínicas que podem se manifestar com esse sintoma, e determinar a etiologia subjacente em cada caso é fundamental para garantir manejo adequado e o melhor desfecho. O objetivo deste artigo é revisar os diagnósticos diferenciais e orientar o manejo de episódios de dispneia aguda.
Acute dyspnea is a common symptom in in-patients. Several clinical conditions can present themselves with this symptom, and determining the subjacent etiology in each case is essential in order to provide the best approach and ensure the best result. The purpose of this paper is to review the differential diagnosis and treatment of acute dyspnea.
Dyspnea , Diagnosis, Differential
A Insuficiência cardíaca com fração de ejeção preservada (ICFEP) é uma síndrome debilitante caracterizada por fração de ejeção preservada (maior que 50%) em pacientes com sintomas de insuficiência cardíaca. É interessante assinalar que, em contraste com insuficiência cardíaca com fração de ejeção reduzida, o manejo de pacientes com ICFEP ainda não foi totalmente estabelecido por diretrizes. O objetivo deste artigo é discutir a fisiopatologia e o manejo dessa síndrome.
Heart failure with preserved ejection fraction (HFpEF) is a debilitating syndrome characterized by a preserved ejection fraction (more than 50%) in patients with symptoms of heart failure. It is interesting to point that in contrast to heart failure with reduced ejection fraction, the management of patients with HFpEF by guidelines has not been totally established yet. This article intends to discuss the physiopathology and management of this syndrome.
Heart Failure , Heart Failure, Diastolic , Therapeutics
A fibrilação atrial é a arritmia cardíaca mais comum e associa-se com importante morbidade e redução no status funcional; além de aumentar o risco de mortalidade por alterações hemodinâmicas, dissincronias atrioventriculares, disfunção mecânica progressiva e complicações tromboembólicas. O manejo da fibrilação de início recente na emergência é o foco desse artigo de revisão.
Atrial fibrillation is the most common cardiac arrythmia and is associate with important morbidity and reduced functional status; besides it increases the mortality because of hemodinamic alteration, atrioventricular dyssynchrony, progressive mechanical disfunction and tromboembolic complications. The management of new onset atrial fibrillation is the aim of this review.
Atrial Fibrillation , Anticoagulants/therapeutic use , Electric Countershock , Emergency Medical Services
As infecções constituem uma causa comum e agravante de morbi-mortalidade em pacientes que apresentam uma ampla variedade de neoplasias malignas. Isto ocorre devido à imunodeficiência gerada tanto por aspectos intrínsecos ao crescimento tumoral como pelo tratamento quimioterápico, que facilita assim a ocorrência de quadros infecciosos graves e muitas vezes de difícil manejo. Orientar a suspeita diagnóstica e o manejo inicial do paciente neutropênico febril são os objetivos desse artigo de revisão.
Infections are a common cause and aggravating factor of morbidity and mortality in patients with a wide variety of malignancies. This occurs because of the immunodeficiency generated either by intrinsic tumor growth by as chemotherapy aspects, so facilitates the occurrence of serious infectious conditions and often difficult to manage. Guide the suspected diagnosis and initial management of febrile neutropenic patients are the aims of this review article.
Drug-Related Side Effects and Adverse Reactions , Febrile Neutropenia/diagnosis , Febrile Neutropenia/therapy , Emergency Medical Services , Neoplasms/drug therapy
