Roles of calcium and Mitochondria-Associated Membranes in the development of obesity and diabetes

Obesity has become a public health problem around the world. According to the Organisation for Economic Co-operation and Development (OECD, 2014 report), more than one in three adults in Mexico are obese. It is known that the hypothalamus, a region of the Central Nervous System (CNS), is actively involved in regulating energy homeostasis during obesity. Anatomically, the hypothalamus is composed of several nuclei coordinating body weight and metabolism, including the arcuate nucleus (ARC), which contains neurons co-expressing orexigenic peptides like Agouti-related protein (AgRP), Neuropeptide Y (NPY) and the anorexigenic peptide Pro-opiomelanocortin (POMC). During obesity, the integration and metabolic response in the ARC is disrupted by three molecular mechanisms: (1) activation of endoplasmic reticulum (ER) stress, (2) mitochondrial dysfunction, and (3) increase of ER and mitochondria contacts, known as Mitochondria-Associated Membranes (MAMs). In this context, it is proposed that MAMs formation induces mitochondrial Ca2+ overload and metabolic dysfunction, leading to insulin resistance and diabetes. Recently, MAMs formation has emerged as one of the molecular mechanisms underlying metabolic alterations during obesity. Thus, in this review we will focus on proposing scientific evidence to support the role of the MAMs and their function on calcium regulation during obesity, as an important pathological mechanism in the development of diabetes mellitus type 2

Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine

Research on mesenchymal stem cells (MSCs) continues to progress rapidly. Nevertheless, the field faces several challenges, such as inherent cell heterogeneity and the absence of unique MSCs markers. Due to MSCs’ ability to differentiate into multiple tissues, these cells represent a promising tool for new cell-based therapies. However, for tissue engineering applications, it is critical to start with a well-defined cell population. Additionally, evidence that MSCs subpopulations may also feature distinct characteristics and regeneration potential has arisen. In this report, we present an overview of the identification of MSCs based on the expression of several surface markers and their current tissue sources. We review the use of MSCs subpopulations in recent years and the main methodologies that have addressed their isolation, and we emphasize the most-used surface markers for selection, isolation, and characterization. Next, we discuss the osteogenic and chondrogenic differentiation from MSCs subpopulations. We conclude that MSCs subpopulation selection is not a minor concern because each subpopulation has particular potential for promoting the differentiation into osteoblasts and chondrocytes. The accurate selection of the subpopulation advances possibilities suitable for preclinical and clinical studies and determines the safest and most efficacious regeneration process

Prenatal cafeteria diet exposure promotes lymphocyte infiltration into the brain and autism-like behavior in the offspring of C57BL6 mice

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an array of etiological causes, including environmental, genetic, and immunological triggers. High-energy diets activate the immune system during prenatal stages favoring infiltration of peripheral immune cells and cytokines into the brain by the choroid plexus and circumventricular regions and altering microglial activity. Accumulation of immune entities and microglia activation in brain have been reported to disrupt social behavior. However, the interplay between prenatal exposure to high-energy diets, neuroinflammation and defective social behavior has not been reported. Methods: Female C57BL6 mice were exposed to cafeteria diet during pregnancy and lactation. The effect of diet on social, locomotor, repetitive-stereotyped, and anxiety-like behavior was evaluated in the male offspring two-month-old. We quantified the number of infiltrating natural killer (NK1.1+), dendritic (CD11c+), lymphocytes (CD11b--CD45+), macrophages (CD11b+-CD45high), and M1 (CD11b+-CD45low-CD86+) or M2 (CD11b+-CD45low-CD206+) microglia in the choroid plexus and cerebral cortex, hippocampus, and striatum of the male offspring by flow cytometry. Results: Our results demonstrated that exposure to cafeteria diet during prenatal stage primed defective social interaction and repetitive-stereotyped behaviors in male offspring. Flow cytometry analysis showed lymphocyte infiltration in the cerebral cortex and hippocampus compared to the choroid plexus in the offspring exposed to cafeteria diet. No significant changes were observed in the NK, dendritic or macrophage levels in the choroid plexus and the cerebral cortex, hippocampus, and striatum regions of those subjects. The effect of cafeteria diet exposure also did not affect microglial density or M1/M2 phenotypes. Conclusions: Our results indicate that exposure to a cafeteria diet during prenatal development promotes an increase of lymphocytes in brain regions of importance for ASD that could contribute to the behavioral defect in the offspring. Testing the contribution of lymphocyte infiltrates in the development of ASD-like behaviors could better explain the cellular mechanisms related to the disorder

Alternative Physical Activation Program to Improve School Performance

One of the problems affecting children in Mexico is the lack of systematic physical activity which influences school performance For this reason the objective was to determine the effect of an alternative physical activation program to improve school performance This was a quantitative study based on a pre-experimental design The participants were N 134 made up of n 64 boys and n 70 girls the average age was 9 4 1 01 Normality tests were applied as well as Student s t-test to compare the results of Bimesters II and IV the confidence level was 95 with a significance value of p 0 05 The most significant results found were in Mathematics p 0 000 in the second and sixth grades Better progress was obtained with the alternative physical activation program to improve school performance the alternative program was used for 40 sessions with a duration of 45 minutes in advance of the school day In conclusion the alternative physical activation program to improve school performance can have a beneficial effect in the subjects of Mathematics Civic Education and Histor

Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine

Research on mesenchymal stem cells (MSCs) continues to progress rapidly. Nevertheless, the field faces several challenges, such as inherent cell heterogeneity and the absence of unique MSCs markers. Due to MSCs' ability to differentiate into multiple tissues, these cells represent a promising tool for new cell-based therapies. However, for tissue engineering applications, it is critical to start with a well-defined cell population. Additionally, evidence that MSCs subpopulations may also feature distinct characteristics and regeneration potential has arisen. In this report, we present an overview of the identification of MSCs based on the expression of several surface markers and their current tissue sources. We review the use of MSCs subpopulations in recent years and the main methodologies that have addressed their isolation, and we emphasize the most-used surface markers for selection, isolation, and characterization. Next, we discuss the osteogenic and chondrogenic differentiation from MSCs subpopulations. We conclude that MSCs subpopulation selection is not a minor concern because each subpopulation has particular potential for promoting the differentiation into osteoblasts and chondrocytes. The accurate selection of the subpopulation advances possibilities suitable for preclinical and clinical studies and determines the safest and most efficacious regeneration process

Fornix volumetric increase during aging associates to microglia activation leading to defective cognitive performance

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration. Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines using the BioPlex platform. We also evaluated the presence of microglia and its morphology. Results: We found a progressive memory loss in an age-dependent manner among in the 12- and 20-months-old mice when compared with the 2-month-old mice. Regarding the MRI, it demonstrated that the fornix volume increased the most and, the left medial entorhinal cortex showed the most volume loss. Microglia number was augmented in fornix and decreased in medial entorhinal cortex which correlated with volume gain or loss, respectively. Microglia morphology was dystrophic and activated in fornix and in a “surveillance” phenotype in the medial entorhinal cortex. We found these phenotypes to be correlated to those volume changes we found in fornix and left medial entorhinal cortex. Conclusions: Here, we selectively identified an age-dependent proinflammatory profile and microglia activation favoring major volumetric brain changes in selective regions associated to cognitive decline in aged mice