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Resumen Introduccion En el mundo, alrededor de 50 millones de personas padecen demencia; la forma mas comun es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo disenar estudios que permitan ampliar el conocimiento sobre su aparicion y desarrollo, para proponer diagnosticos tempranos y/o posibles tratamientos. Una de las estrategias metodologicas que se han desarrollado son los modelos transgenicos murinos para el estudio de los factores involucrados en su etiologia, y entre ellos, el estres oxidativo y la respuesta inmune. Desarrollo Se realizo una busqueda de articulos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revision abordamos dos factores que han sido estudiados de forma independiente: el estres oxidativo y la respuesta inmune en modelos transgenicos para la EA, y se discute la relacion que existe entre ellos y que impacta en la perdida de la plasticidad sinaptica y estructural, produciendo como efecto final el deterioro cognitivo. Conclusion Esta revision describe posibles mecanismos en donde participan el estres oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relacion entre estos elementos que conducen hacia el deterioro cognitivo.

In marked contrast to the ample literature showing that the dorsal striatum is engaged in memory consolidation, little is known about its involvement in memory retrieval. Recent findings demonstrated significant increments in dendritic spine density and mushroom spine counts in dorsal striatum after memory consolidation of moderate inhibitory avoidance (IA) training; further increments were found after strong training. Here, we provide evidence that in this region spine counts were also increased as a consequence of retrieval of moderate IA training, and even higher mushroom spine counts after retrieval of strong training; by contrast, there were fewer thin spines after retrieval. Similar changes in mushroom and thin spine populations were found in the ventral striatum (nucleus accumbens), but they were related to the aversive stimulation and not to memory retrieval. These results suggest that memory retrieval is a dynamic process which produces neuronal structural plasticity that might be necessary for maintaining or strengthening assemblies that encode stored information.

The irreversible and progressive neurodegenerative Alzheimer’s disease (AD) is characterized by cognitive decline, extracellular β-amyloid peptide accumulation, and tau neurofibrillary tangles in the cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls [non-transgenic mice (NoTg)], at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.

Typical amnestic treatments are ineffective when administered to subjects trained in aversively-motivated tasks using relatively high foot-shock intensities. This effect has been found when treatments that disrupt neuronal activity are administered to different regions of the brain, including the amygdala. However, the molecular mechanisms induced by this intense training are unknown. We made a detailed mapping of c-Fos-expressing neurons in four regions of the amygdala after moderate and intense one-trial inhibitory avoidance training. Rats were sacrificed 90 min after training or after appropriate control procedures, and their brains were prepared for immunohistochemical c-Fos protein detection in the central, lateral, and in the anterior and posterior parts of the basolateral amygdaloid nucleus. We found a high percentage of neurons expressing c-Fos in the anterior part of the basolateral nucleus after moderate training, and this percentage increased further after intense training. Moderate and intense training did not induce changes in c-Fos expression in the other explored amygdaloid regions. These results show that inhibitory avoidance training produces a localized expression of c-Fos in the basolateral anterior nucleus of the amygdala, which is dependent upon the intensity of training, and indicate that synaptic plastic changes in this region may be required for the formation of memory of moderate and intense aversive learning.

The hippocampus plays a fundamental role in spatial learning and memory. Dentate gyrus (DG) granular neurons project mainly to proximal apical dendrites of neurons in the CA3 stratum lucidum and also, to some extent, to the basal dendrites of CA3 pyramidal cells in the stratum oriens. The terminal specializations of DG neurons are the mossy fibers (MF), and these huge axon terminals show expansion in the CA3 stratum oriens after the animals undergo overtraining in the Morris Water Maze task (MWM). However, to our knowledge there are no reports regarding the possible changes in density of post-synaptic targets of these terminals in the basal dendrites of CA3 neurons after overtraining in the MWM. The purpose of this work was to study the density of thorny excrescences (TE) and other dendritic spine types (stubby, thin, and mushroom) in the CA3 stratum oriens in animals overtrained in the MWM for three consecutive days and in animals trained for only one day. Seven days after MWM training, the animals were sacrificed, and their brains removed and processed for rapid Golgi staining to visualize the different types of dendritic protrusions. Our results revealed that the relative quantity of stubby, thin, and mushroom dendritic spines did not change, regardless of amount of training. However, a significant increase in the density of TE was detected in the overtrained animals. These results strongly suggest that spatial water maze overtraining induces an increased density of MF–TE connections, which might be functionally relevant for long-term spatial memory formation. Fil: Gómez Padilla, Eurídice. Universidad Autonoma de Queretaro.; México Fil: Bello Medina, Paola C.. Universidad Nacional Autónoma de México; México Fil: León Jacinto, Uriel. Universidad Nacional Autónoma de México; México Fil: Orta Salazar, Erika. Universidad Nacional Autónoma de México; México Fil: Quirarte, Gina L.. Universidad Nacional Autónoma de México; México Fil: Ramirez Amaya, Victor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Autonoma de Queretaro.; México Fil: Prado Alcalá, Roberto A.. Universidad Nacional Autónoma de México; México Fil: Díaz Cintra, Sofía. Universidad Nacional Autónoma de México; México

The growth of many cities has generated an increase in the emission of environmental pollutants. Exposure to these pollutants has been associated with increased mortality worldwide. These pollutants, such as ozone, produce reactive oxygen species (ROS), which cause oxidative stress throughout the body. It has been observed that there is a relationship between chronic oxidative stress and the development of degenerative diseases typical of old age such as amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease. The purpose of this research was to evaluate whether chronic exposure to ozone produces a deleterious effect on density and morphology of dendritic spines in CA1 of dorsal hippocampus and on learning and memory of object–place recognition. Rats were exposed to ozone or to ozone-free air for a period of 15, 30, 60, or 90 days. The principal results indicate that chronic oxidative stress induced by ozone produces a decrease in the density of dendritic spines, a decrease in thin and mushroom spine ratios, and an increase in stubby spine ratio, as well as a deficit in learning and memory of the object–place recognition task. These results indicate that chronic ozone exposure produces a loss in the inputs of CA1 neurons of the dorsal hippocampus, which may be the source of the cognitive deficits observed in the object–place recognition task, as indicated by the decrease in density of dendritic spines; these alterations are similar to those reported in some neurodegenerative diseases such as Alzheimer's disease.

Adult-born neurons in the dentate gyrus (DG) functionally integrate into the behaviorally relevant hippocampal networks, showing a specific Arc-expression response to spatial exploration when mature. However, it is not clear when, during the 4- to 6-week interval that is critical for survival and maturation of these neurons, this specific response develops. Therefore, we characterized Arc expression after spatial exploration or cage control conditions in adult-born neurons from rats that were injected with BrdU on one day and were sacrificed 1, 7, 15, 30, and 45 days post-BrdU injection (PBI). Triple immunostaining for NeuN, Arc, and BrdU was analyzed through the different DG layers. Arc protein expression in BrdU-positive cells was observed from day 1 to day 15 PBI but was not related to behavioral stimulation. The specific Arc-expression response to spatial exploration was observed from day 30 and 45 in about 5% of the BrdU-positive cell population. Most of the BrdU-positive neurons expressing Arc in response to spatial exploration (∼90%) were located in DG layer 1, and no Arc expression was observed in cells located in the subgranular zone (SGZ). Using the current data and that obtained previously, we propose a mathematical model suggesting that new neurons are unlikely to respond to exploration by expressing Arc after they are 301 days old, and also that in a 7-month-old rat the majority (60%) of the neurons that respond to exploration must have been born during adulthood; thus, suggesting that adult neurogenesis in the DG is highly relevant for spatial information processing.