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Resumen Introduccion La sobrepoblacion y el crecimiento industrial causan un aumento en la contaminacion del aire, principalmente de particulas suspendidas y en la formacion de ozono. La exposicion repetida a bajas dosis de ozono, como la de un dia con alta contaminacion del aire, genera un estado de estres oxidativo cronico, el cual causa perdida de espinas dendriticas, alteraciones en la plasticidad cerebral y en los mecanismos de aprendizaje y memoria, asi como muerte neuronal y perdida de la capacidad de reparacion cerebral. Esto tiene un impacto directo en la salud humana, aumentando la incidencia de enfermedades cronico-degenerativas. Desarrollo Se realizo una busqueda de articulos originales y revisiones en PubMed, Scopus y Google Scholar (2000-2018) sobre las principales consecuencias de la exposicion a ozono, sobre la plasticidad sinaptica, sobre el procesamiento de la informacion en los procesos cognitivos y sobre las alteraciones que pueden llevar al desarrollo de enfermedades neurodegenerativas. Conclusiones Esta revision describe uno de los mecanismos fisiopatologicos del efecto de la exposicion repetida a bajas dosis de ozono, a traves de producir un estado de estres oxidativo cronico, lo cual causa perdida de la plasticidad sinaptica; esta funcion cerebral es clave tanto en el procesamiento de informacion como en la generacion de cambios estructurales en las poblaciones neuronales. Tambien se aborda el efecto de la exposicion cronica a ozono sobre el tejido cerebral, y la estrecha relacion entre la contaminacion por ozono y la aparicion y evolucion de las enfermedades neurodegenerativas.

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 most influential hypothesis about the neurobiological basis of memory consolidation posits that this process is dependent upon de novo protein synthesis. Strong support for this proposition has been provided by a multitude of experiments showing that protein synthesis inhibitors (PSIs) interfere with consolidation. However, this hypothesis has been challenged by the results of studies showing that PSIs also produce a host of side effects that, by themselves, could account for their amnestic effects. It has been demonstrated that amnestic treatments become innocuous when administered to animals that have been subjected to intense training in a variety of learning tasks. We now report that while infusion of anisomycin (ANI), a PSI, into the dorsal striatum (DS) impairs memory consolidation of inhibitory avoidance learning in response to moderate aversive stimuli, such impairment by ANI is overcome by application of an intense stimulus. We also confirmed that ANI induces inhibition of protein synthesis in the DS, as evidenced by a reduction of the activity-regulated cytoskeletal associated protein (Arc). We found, for the first time, that ANI also induces an increased concentration of serotonin in the DS, which, by itself, may account for the interference with memory consolidation. These findings suggest that de novo protein synthesis in the dorsal striatum is not necessary for the consolidation of intense emotionally arousing experiences. The possibility of a non-genomic-dependent mechanism of memory consolidation is discussed.

The long-standing hypothesis that memory consolidation is dependent upon de novo protein synthesis is based primarily on the amnestic effects of systemic administration of protein synthesis inhibitors (PSIs). Early experiments on mice showed that PSIs produced interference with memory consolidation that was dependent on the doses of PSIs, on the interval between drug injection and training, and, importantly, on the degree and duration of protein synthesis inhibition in the brain. Surprisingly, there is a conspicuous lack of information regarding the relationship between the duration of protein synthesis inhibition produced by PSIs and memory consolidation in the rat, one of the species most widely used to study memory processes. We found that, in the male rat, a single injection of cycloheximide, a commonly used PSI, produced a significant imbalance in protein homeostasis: an early inhibition of protein synthesis that lasted for at least one hour, followed by hyperproduction of proteins that lasted three days. We evaluated memory consolidation of inhibitory avoidance trained with either low or high intensity of foot-shock at the peaks of protein synthesis inhibition and protein hyperproduction. We found that, independent of the moment of training, the low-foot-shock groups showed amnesia, while the high-foot-shock groups displayed optimal memory performance. These results indicate that memory consolidation of relatively weak training is impaired by the inhibition or hyperproduction of protein synthesis, and that intense training overcomes this dysregulation of protein homeostasis allowing for memory formation probably through non-genomic mechanisms.

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.

Findings of several experiments indicate that many treatments that typically interfere with memory consolidation are ineffective in preventing or attenuating memory induced by intense training. As extensive evidence suggests that the consolidation of newly acquired memories requires gene expression and de novo protein synthesis the present study investigated whether intense training prevents consolidation impairment induced by blockers of mRNA and protein synthesis. Rats were given a single inhibitory training trial using a moderate (1.0 mA) or a relatively intense (2.0 mA) foot-shock. Bilateral hippocampal infusions of the mRNA synthesis blocker DRB (10, 40 or 80 ng/0.5 µL/hemisphere) or the protein synthesis inhibitor anisomycin (ANI), an inhibitor de novo protein synthesis (15.62, 31.25, or 62.50 µg/0.5 µL/hemisphere) were administered 15 min prior to training. Retention was measured at 30 min or 48 h following training. DRB and ANI impaired memory of moderate training in a dose-dependent manner without affecting short-term memory. In contrast, memory consolidation was not impaired in the groups trained with 2.0 mA. The findings showed that: (1) inhibitors of transcription and translation in the hippocampus impair the consolidation of memory of inhibitory avoidance learning induced by moderate levels of aversive stimulation and (2) blocking of mRNA and protein synthesis does not prevent the consolidation of memory induced by relatively high levels of aversive stimulation. These findings do not support the hypothesis that gene expression and de novo protein synthesis are necessary steps for long-term memory formation as memory was not impaired if intense foot-shock was used in training.

A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information.