High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View

Alzheimer’s disease is the most common type of dementia in occidental countries. The majority of the cases develop the disease for no genetic reasons; therefore, it is crucial to establish which environmental factors trigger the development of the disease. It has been proposed that nutritional habits, especially main components of Western countries’ diet such as saturated fat or cholesterol, increase the risk for development of Alzheimer’s disease (AD) and/or accelerate the onset of the disease, which is a big concern in countries where obesity is a public health problem. It is crucial to understand the links between alimentary habits and the development of AD and other types of dementia. A possible mechanism is the disruption of blood–brain barrier (BBB), which is the protection of the brain from circulating blood. Such disruptions can result from consuming high-fat diet (HFD) or high-cholesterol diet (HCD) and inflammation produced by alteration in brain vasculature resulted for chronic consumption of such type of diets. What has named a "Systemic view" comprises the idea that; what happens outside of the brain environment does affect brain functioning and the modifications experienced in the brain environment resulted from the influence of external factors will affect the entire body. In the current chapter, we will review the state of the art in the studies of the impact of a diet rich in fat or cholesterol on the brain and how the alterations induced in other organs can impact brain functioning increasing the susceptibility of development of dementia

Alzheimer’s Disease and Type 2 Diabetes Mellitus: Molecular Mechanisms and Similarities

Alzheimer’s disease (AD) has become one of the most threatening diseases in the elderly, and type 2 diabetes mellitus (T2DM) is a major health problem in the world, representing 7.4% of the population. Several studies have produced epidemiological, clinical, and pathological evidence of the relationship between AD and T2DM. Laboratory research using animal models has identified mechanisms shared by both T2DM and AD. Particularly, there is an increase of tau phosphorylation and cleavage, which is known to be particularly toxic to neurons and to form a nucleation for neurofibrillary tangles. Also, alterations in synaptic plasticity are associated to tau pathology through the direct abnormal interaction of pathological tau with synaptic proteins and indirectly through Tau-activated neuroinflammatory processes. Many T2DM complications are potentiated or initiated by the accumulation of specific forms of advanced glycation end products (AGEs) and their interaction with its receptors (RAGE). AGEs promote β-amyloid aggregation and cytotoxicity, while glycation of tau may enhance their aggregation. Therefore, this review addresses the analysis of the common mechanisms where the major molecular players of these two diseases participate and contribute to a better understanding of these diseases in their pathogenic relationship

Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of Mexico

This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which were compared to other Mestizo and parental (Amerindian, European and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point towards a European ancestry, where the R1b was the most frequent. In addition, important frequencies of Amerindian linages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (x M3) and M3. However, even within each lineage a high diversity was found despite the small number of samples bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications

Mesa de Reflexión: Internet como Derecho Ciudadano y Acceso a La Red Nacional de Educación e Investigación (RNEI)

Mesa de Reflexión: Internet como Derecho Ciudadano y Acceso a la RNIE 3/5 El uso de Internet e Internet 2 en el CINVESTAV" Dr. Marco Antonio Meraz Ríos, Secretario de Planeación del Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV). "El uso de Internet e Internet 2 en la UNAM" Act. Fabián Romo Zamudio, Director de Sistemas y Servicios Institucionales de la Dirección General de Cómputo y de Tecnologías de Información y Comunicación de la UNAM. "El uso de Internet e Internet 2 en la Universidad de Colima" M.C. Jorge Enrique Preciado Velasco, Coordinador de Redes de la Universidad de Colima.El uso de Internet e Internet 2 en el CINVESTAV; El uso de Internet e Internet 2 en la Universidad Nacional Autónoma de México (UNAM); El uso de Internet e Internet 2 en la Universidad de Colima (UCOL)VTS_03_1.av

Early Onset Alzheimer’s Disease and Oxidative Stress

Alzheimer’s disease (AD) is the most common cause of dementia in elderly adults. It is estimated that 10% of the world’s population aged more than 60–65 years could currently be affected by AD, and that in the next 20 years, there could be more than 30 million people affected by this pathology. One of the great challenges in this regard is that AD is not just a scientific problem; it is associated with major psychosocial and ethical dilemmas and has a negative impact on national economies. The neurodegenerative process that occurs in AD involves a specific nervous cell dysfunction, which leads to neuronal death. Mutations in APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have demonstrated that alterations in these proteins are able to induce oxidative damage, which in turn favors the development of AD. This paper provides a review of many, although not all, of the mutations present in patients with familial Alzheimer’s disease and the association between some of these mutations with both oxidative damage and the development of the pathology

Distinct Transcriptional Profile of PDZ Genes after Activation of Human Macrophages and Dendritic Cells

The PDZ (PSD95, Dlg and ZO-1) genes encode proteins that primarily function as scaffolds of diverse signaling pathways. To date, 153 PDZ genes have been identified in the human genome, most of which have multiple protein isoforms widely studied in epithelial and neural cells. However, their expression and function in immune cells have been poorly studied. Herein, we aimed to assess the transcriptional profiles of 83 PDZ genes in human macrophages (Mɸ) and dendritic cells (DCs) and changes in their relative expression during cell PRR stimulation. Significantly distinct PDZ gene transcriptional profiles were identified under different stimulation conditions. Furthermore, a distinct PDZ gene transcriptional signature was found in Mɸ and DCs under the same phagocytic stimuli. Notably, more than 40 PDZ genes had significant changes in expression, with potentially relevant functions in antigen-presenting cells (APCs). Given that several PDZ proteins are targeted by viral products, our results support that many of these proteins might be viral targets in APCs as part of evasion mechanisms. Our results suggest a distinct requirement for PDZ scaffolds in Mɸ and DCs signaling pathways activation. More assessments on the functions of PDZ proteins in APCs and their role in immune evasion mechanisms are needed

Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f), during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV). By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60%) and multipolar Glutamatergic (≤40%) neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC): dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively), in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles) of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures