Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.     

Obstructive Sleep Apnea Syndrome (OSAS). Review of the literature

Obstructive sleep apnea and hypopnea syndrome is characterized by repeated airway collapse during sleep. The li-terature describes multiple causes of the disease. The main cause is a reduction of the expansion forces of the pharyngeal dilator muscles, as in situations of genioglossal muscle dysfunction, and discoordination between the inspiratory activity of the muscle and respiratory effort, which play an important role in progression of the disease. Other described causes are soft tissue disorders, such as macroglossia or tonsillar hypertrophy, and skeletal structural alterations such as micrognathia and retrognathia. The syndrome is also more frequent in obese people, where the accumulation of fat in the neck region produces narrowing of the pharyngeal airway, thereby diminishing the passage of air. This review focuses on the pathogenesis, epidemiology, main features and diagnosis of the disease, and on its main forms of treatment. Key words:Sleep apnea, obstructive sleep apnea, sleep apnea syndrome, obstructive sleep apnea syndrome.     

P300 latency and amplitude in Alzheimer's disease: a systematic review

The P300 plays a key role as a method for monitoring and evaluating dementia, including Alzheimer's disease.Objective: The goal of this study was to search for articles which analyzed P300 latency and amplitude values in Alzheimer's disease.Methods: We searched in the following databases: Web of Science, Pub Med, Psyc Info, Medline, Biological Abstracts and Scielo using the following keywords: speed of information processing, processing speed, information processing, aged, older, elderly, older people, alzheimer dementia, alzheimer disease, Alzheimer and cross-references of selected articles.Results: We found eight studies matching the inclusion criteria. These studies showed that there is a consensus on a P300 latency increase of elderly patients with Alzheimer's disease compared with subjects without the disease. However, it appears that, with respect to the P300 amplitude, there is still no consensus; however, it may be related to different methodological variables adopted in the reviewed studies.Conclusion: There is a need to standardize the variables involved in P300 measurement for senior citizens with Alzheimer's disease in order to be able to compare P300 latency and amplitude values for this population.     

The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate,iodoacetate or 5-fluorouracil

Background  

Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H⁺-ATPase (β-F1-ATPase). The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU).     

Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance

Cardiac remodeling (CR) is a structural change of the heart due to chronic hemodynamic overload related to changes in both myocyte and extracellular matrix (ECM). We investigated that the imbalance of collagen V promotes cardiomyocyte apoptosis that contributes to heart failure and cell death. Aortic stenosis was induced surgically and male Wistar rats were randomized to 18 weeks (Sham 18?w, n?=?12; AoS 18?w, n?=?12) and severe of heart failure (Sham HF, n?=?12; AoS HF, n?=?12) groups. Functional and structural echocardiogram, immunohistochemistry for Ki-67, TUNEL assay and Immunofluorescence for collagen were performed. Our main results were: (1) Progressive reduction of cardiac functional capacity due to cardiac remodeling with decreased eject fraction in heart failure; (2) Imbalance of collagen deposition with increased, crowded and irregular collagen I in situ expression; (3) Dysregulation of dynamic control of collagen fibers with exposed epitopes of collagen V; (4) Additional apoptosis that are dependent to cardiac injury. The collagen V expression in cardiac remodeling is for the first time described and may be related to additional apoptosis and autoimmune response. Our findings suggest a critical role of collagen V in cardiac remodeling to modulate and promote heart failure and death.