Ozone pollution, oxidative stress, synaptic plasticity, and neurodegeneration.

INTRODUCTION: Overpopulation and industrial growth result in an increase in air pollution, mainly due to suspended particulate matter and the formation of ozone. Repeated exposure to low doses of ozone, such as on a day with high air pollution levels, results in a state of chronic oxidative stress, causing the loss of dendritic spines, alterations in cerebral plasticity and in learning and memory mechanisms, and neuronal death and a loss of brain repair capacity. This has a direct impact on human health, increasing the incidence of chronic and degenerative diseases. DEVELOPMENT: We performed a search of the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2000 and 2018 and addressing the main consequences of ozone exposure on synaptic plasticity, information processing in cognitive processes, and the alterations that may lead to the development of neurodegenerative diseases. CONCLUSIONS: This review describes one of the pathophysiological mechanisms of the effect of repeated exposure to low doses of ozone, which causes loss of synaptic plasticity by producing a state of chronic oxidative stress. This brain function is key to both information processing and the generation of structural changes in neuronal populations. We also address the effect of chronic ozone exposure on brain tissue and the close relationship between ozone pollution and the appearance and progression of neurodegenerative diseases.

Effect of exposure to low doses of ozone on interleukin 17A expression during progressive neurodegeneration in the rat hippocampus.

INTRODUCTION: Chronic exposure to low doses of ozone causes oxidative stress and loss of regulation of the inflammatory response, leading to progressive neurodegeneration. OBJECTIVE: We studied the effect of chronic exposure to low doses of ozone on IL-17A concentration and expression in neurons, microglia, astrocytes, and T cells in the rat hippocampus. METHODS: We used 72 Wistar rats, divided into 6 groups (n=12): a control group (no ozone exposure) and 5 groups exposed to ozone (0.25ppm, 4h daily) for 7, 15, 30, 60, and 90 days. We processed 6 rats from each group to quantify IL-17A by ELISA; the remaining 6 were processed for immunohistochemistry (against IL-17A and GFAP, Iba1, NeuN, and CD3). RESULTS: The ELISA study data showed a significant increase in IL-17A concentrations in the 7-, 15-, 30-, and 60-day exposure groups, with regard to the control group (P<.05). Furthermore, they indicate that hippocampal neurons were the cells showing greatest immunoreactivity against IL-17A between 60 and 90 days of exposure to ozone; we also observed an increase in activated astrocytes in the 30- and 60-day exposure groups. CONCLUSION: Exposure to ozone in rats induces an increase in IL-17A expression, mainly in hippocampal neurons, accompanied by hippocampal astrocyte activation during chronic neurodegeneration, similar to that observed in Alzheimer disease in humans.

La respuesta sistémica Th17/IL-17A aparece antes del proceso neurodegenerativo en el hipocampo de ratas expuestas a bajas dosis de ozono / Systemic Th17/IL-17A response appears prior to hippocampal neurodegeneration in rats exposed to low doses of ozone

Introducción: La exposición a dosis bajas de O3 conduce a un estado de estrés oxidativo. Algunos estudios muestran que el estado de estrés oxidativo puede modular tanto el SNC como la inflamación sistémica, que son importantes para el desarrollo de la enfermedad de Alzheimer. Objetivo: Evaluar la frecuencia de células tipo Th17, la concentración de IL-17A en plasma y la inmunorreactividad del hipocampo a IL-17A en ratas expuestas a dosis bajas de O3.Métodos: Ciento ocho ratas Wistar machos fueron divididas en 6 grupos (n = 18) con los siguientes tratamientos: control (sin O3) y O3 (0,25 ppm, diario por 4h) durante 7, 15, 30, 60 y 90 días. De cada grupo se decapitaron 12 animales, se tomó una muestra de sangre periférica para aislar el plasma y las células mononucleares. La IL-17A plasmática se evaluó mediante LUMINEX y la frecuencia de células de tipo Th17 por citometría de flujo. Las ratas restantes se anestesiaron y se perfundieron para inmunohistoquímica en el hipocampo. Resultados: Muestran que la exposición durante 7 días a O3 produce un aumento significativo en la frecuencia de células tipo Th17 y los niveles de IL-17A en sangre periférica. Sin embargo, existe una disminución de Th17/IL-17A en la periferia desde el día 15. También se encontró un aumento de IL-17A en el hipocampo desde los 30 días de exposición. Conclusión: El O3 produce un efecto sistémico a corto plazo de tipo Th17/IL-17A y un aumento de IL-17A en el tejido del hipocampo durante el proceso neurodegenerativo crónico

Introduction: Exposure to low doses of O3 leads to a state of oxidative stress. Some studies show that oxidative stress can modulate both the CNS and systemic inflammation, which are important factors in the development of Alzheimer disease (AD).Objective: This study aims to evaluate changes in the frequency of Th17-like cells (CD3+CD4+IL-17A+), the concentration of IL-17A in peripheral blood, and hippocampal immunoreactivity to IL-17A in rats exposed to low doses of O3. Methods: One hundred eight male Wistar rats were randomly assigned to 6 groups (n = 18) receiving the following treatments: control (O3 free) or O3 exposure (0.25 ppm, 4hours daily) over 7, 15, 30, 60, and 90 days. Twelve animals from each group were decapitated and a peripheral blood sample was taken to isolate plasma and mononuclear cells. Plasma IL-17A was quantified using LUMINEX, while Th17-like cells were counted using flow cytometry. The remaining 6 rats were deeply anaesthetised and underwent transcardial perfusion for immunohistological study of the hippocampus. Results: Results show that exposure to O3 over 7 days resulted in a significant increase in the frequency of Th17-like cells and levels of IL-17A in peripheral blood. However, levels of Th17/IL-17A in peripheral blood were lower at day 15 of exposure. We also observed increased IL-17A in the hippocampus beginning at 30 days of exposure. Conclusion: These results indicate that O3 induces a short-term, systemic Th17-like/IL-17A effect and an increase of IL-17A in the hippocampal tissue during the chronic neurodegenerative process

Ozone pollution, oxidative stress, synaptic plasticity, and neurodegeneration. / Contaminación por ozono, estrés oxidativo, plasticidad sináptica y neurodegeneración.

INTRODUCTION: Overpopulation and industrial growth result in an increase in air pollution, mainly due to suspended particulate matter and the formation of ozone. Repeated exposure to low doses of ozone, such as on a day with high air pollution levels, results in a state of chronic oxidative stress, causing the loss of dendritic spines, alterations in cerebral plasticity and in learning and memory mechanisms, and neuronal death and a loss of brain repair capacity. This has a direct impact on human health, increasing the incidence of chronic and degenerative diseases. DEVELOPMENT: We performed a search of the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2000 and 2018 and addressing the main consequences of ozone exposure on synaptic plasticity, information processing in cognitive processes, and the alterations that may lead to the development of neurodegenerative diseases. CONCLUSIONS: This review describes one of the pathophysiological mechanisms of the effect of repeated exposure to low doses of ozone, which causes loss of synaptic plasticity by producing a state of chronic oxidative stress. This brain function is key to both information processing and the generation of structural changes in neuronal populations. We also address the effect of chronic ozone exposure on brain tissue and the close relationship between ozone pollution and the appearance and progression of neurodegenerative diseases.

Effect of Ozone Exposure on Dendritic Spines of CA1 Pyramidal Neurons of the Dorsal Hippocampus and on Object-place Recognition Memory in Rats.

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.

Systemic Th17/IL-17A response appears prior to hippocampal neurodegeneration in rats exposed to low doses of ozone. / La respuesta sistémica Th17/IL-17A aparece antes del proceso neurodegenerativo en el hipocampo de ratas expuestas a bajas dosis de ozono.

INTRODUCTION: Exposure to low doses of O3 leads to a state of oxidative stress. Some studies show that oxidative stress can modulate both the CNS and systemic inflammation, which are important factors in the development of Alzheimer disease (AD). OBJECTIVE: This study aims to evaluate changes in the frequency of Th17-like cells (CD3+CD4+IL-17A+), the concentration of IL-17A in peripheral blood, and hippocampal immunoreactivity to IL-17A in rats exposed to low doses of O3. METHODS: One hundred eight male Wistar rats were randomly assigned to 6 groups (n=18) receiving the following treatments: control (O3 free) or O3 exposure (0.25ppm, 4hours daily) over 7, 15, 30, 60, and 90 days. Twelve animals from each group were decapitated and a peripheral blood sample was taken to isolate plasma and mononuclear cells. Plasma IL-17A was quantified using LUMINEX, while Th17-like cells were counted using flow cytometry. The remaining 6 rats were deeply anaesthetised and underwent transcardial perfusion for immunohistological study of the hippocampus. RESULTS: Results show that exposure to O3 over 7 days resulted in a significant increase in the frequency of Th17-like cells and levels of IL-17A in peripheral blood. However, levels of Th17/IL-17A in peripheral blood were lower at day 15 of exposure. We also observed increased IL-17A in the hippocampus beginning at 30 days of exposure. CONCLUSION: These results indicate that O3 induces a short-term, systemic Th17-like/IL-17A effect and an increase of IL-17A in the hippocampal tissue during the chronic neurodegenerative process.

Effect of exposure to low doses of ozone on interleukin 17A expression during progressive neurodegeneration in the rat hippocampus. / Efecto de la exposición a bajas dosis de ozono en la expresión de la interleucina 17A durante el proceso de neurodegeneración progresiva en el hipocampo de ratas.

INTRODUCTION: Chronic exposure to low doses of ozone causes oxidative stress and loss of regulation of the inflammatory response, leading to progressive neurodegeneration. OBJECTIVE: We studied the effect of chronic exposure to low doses of ozone on IL-17A concentration and expression in neurons, microglia, astrocytes, and T cells in the rat hippocampus. METHODS: We used 72 Wistar rats, divided into 6 groups (n=12): a control group (no ozone exposure) and 5 groups exposed to ozone (0.25ppm, 4h daily) for 7, 15, 30, 60, and 90 days. We processed 6 rats from each group to quantify IL-17A by ELISA; the remaining 6 were processed for immunohistochemistry (against IL-17A and GFAP, Iba1, NeuN, and CD3). RESULTS: The ELISA study data showed a significant increase in IL-17A concentrations in the 7-, 15-, 30-, and 60-day exposure groups, with regard to the control group (P<.05). Furthermore, they indicate that hippocampal neurons were the cells showing greatest immunoreactivity against IL-17A between 60 and 90 days of exposure to ozone; we also observed an increase in activated astrocytes in the 30- and 60-day exposure groups. CONCLUSION: Exposure to ozone in rats induces an increase in IL-17A expression, mainly in hippocampal neurons, accompanied by hippocampal astrocyte activation during chronic neurodegeneration, similar to that observed in Alzheimer disease in humans.

Coleoptera Associated with Decaying Wood in a Tropical Deciduous Forest.

Coleoptera is the largest and diverse group of organisms, but few studies are dedicated to determine the diversity and feeding guilds of saproxylic Coleoptera. We demonstrate the diversity, abundance, feeding guilds, and succession process of Coleoptera associated with decaying wood in a tropical deciduous forest in the Mixteca Poblana, Mexico. Decaying wood was sampled and classified into four stages of decay, and the associated Coleoptera. The wood was identified according to their anatomy. Diversity was estimated using the Simpson index, while abundance was estimated using a Kruskal-Wallis test; the association of Coleoptera with wood species and decay was assessed using canonical correspondence analysis. Decay wood stage I is the most abundant (51%), followed by stage III (21%). We collected 93 Coleoptera belonging to 14 families, 41 genera, and 44 species. The family Cerambycidae was the most abundant, with 29% of individuals, followed by Tenebrionidae with 27% and Carabidae with 13%. We recognized six feeding guilds. The greatest diversity of Coleoptera was recorded in decaying Acacia farnesiana and Bursera linanoe. Kruskal-Wallis analysis indicated that the abundance of Coleoptera varied according to the species and stage of decay of the wood. The canonical analysis showed that the species and stage of decay of wood determined the composition and community structure of Coleoptera.

Oxidative stress caused by ozone exposure induces ß-amyloid 1-42 overproduction and mitochondrial accumulation by activating the amyloidogenic pathway.

Oxidative stress is a major risk factor for Alzheimer's disease (AD) that has been suggested to be the trigger of AD pathology. However, whether oxidative damage precedes and contributes directly to the intracellular accumulation of beta amyloid 1-42 (ßA42) peptide remains a matter of debate. Chronic exposure to low doses of ozone similar to the levels during a day of high pollution in México City causes a state of oxidative stress that elicits progressive neurodegeneration in the hippocampi of rats. Several reports have demonstrated that the mitochondria are among the first organelles to be affected by oxidative stress and ßA42 toxicity and act as sites of the accumulation of ßA42, which affects energy metabolism. However, the mechanisms related to the neurodegeneration process and organelle damage that occur in conditions of chronic exposure to low doses of ozone have not been demonstrated. To analyze the effect of chronic ozone chronic exposure on changes in the production and accumulation of the ßA42 and ßA40 peptides in the mitochondria of hippocampal neurons of rats exposed to ozone, we examined the mitochondrial expression levels of Presenilins 1 and 2 and ADAM10 to detect changes related to the oxidative stress caused by low doses of ozone (0.25ppm). The results revealed significant accumulations of ßA42 peptide in the mitochondrial fractions on days 60 and 90 of ozone exposure along with reductions in beta amyloid 1-40 accumulation, significant overexpressions of Pres2 and significant reductions in ADAM10 expression. Beta amyloid immunodetection revealed that there were some intracellular deposits of ßA42 and that ßA42 and the mitochondrial markers OPA1 and COX1 colocalized. These results indicate that the time of exposure to ozone and the accumulation of ßA42 in the mitochondria of the hippocampal cells of rats were correlated. Our results suggest that the accumulation of the ßA42 peptide may promote mitochondrial dysfunction due to its accumulation and overproduction.

Tibolone prevents oxidation and ameliorates cholinergic deficit induced by ozone exposure in the male rat hippocampus.

Oxidative stress is related to the development of central nervous system diseases involving memory processes. Cholinergic system and memory processes are disrupted by ozone exposure. In rats, ozone induces motor disturbances and memory deficits as well as biochemical changes in brain regions related to memory processes. In this work, we analyzed the effect of chronic tibolone (TIB) administration in central nervous system, specifically the content of choline acetyltransferase, acetylcholinesterase, acetylcholine and oxidative stress markers in the hippocampus of male rats exposed to ozone. Our results reveal a neuroprotective effect of TIB treatment on neuronal damage induced by chronic ozone exposure. Furthermore, we suggest that TIB can prevent memory deficits by providing a protective effect against oxidative stress and the cholinergic system disruption induced by ozone exposure. Together, these findings present a potential neuroprotective effect of TIB in processes linked to memory deficits induced by aging or neurodegenerative diseases.

Quaternary origin and genetic divergence of the endemic cactus Mammillaria pectinifera in a changing landscape in the Tehuacán Valley, Mexico.

The endemic Mexican cactus, Mammillaria pectinifera, shows low dispersal capabilities and isolated populations within the highly dissected landscape of Tehuacán Valley. These characteristics can restrict gene flow and act upon the genetic divergence and speciation in arid plants. We conducted a phylogeographic study to determine if the origin, current distribution, and genetic structure of M. pectinifera were driven by Quaternary geomorphic processes. Sequences of the plastids psbA-trnH and trnT-trnL obtained from 66 individuals from seven populations were used to estimate genetic diversity. Population differentiation was assessed by an analysis of molecular variance. We applied a stepwise phylogenetic calibration test to determine whether species origin and genetic divergence among haplotypes were temporally concordant with recognizable episodes of geomorphic evolution. The combination of plastid markers yielded six haplotypes, with high levels of haplotype diversity (h = 0.622) and low nucleotide diversity (π = 0.00085). The populations were found to be genetically structured (F(ST) = 0.682; P < 0.00001), indicating that geographic isolation and limited dispersal were the primary causes of genetic population differentiation. The estimated origin and divergence time among haplotypes were 0.017-2.39 and 0.019-1.237 mya, respectively, which correlates with Pleistocene tectonics and erosion events, supporting a hypothesis of geomorphically-driven geographical isolation. Based on a Bayesian skyline plot, these populations showed long term demographic stability, indicating that persistence in confined habitats has been the main response of this species to landscape changes. We conclude that the origin and haplotype divergence of M. pectinifera were a response to local Quaternary geomorphic evolution.

Mitochondrial dysfunction in the hippocampus of rats caused by chronic oxidative stress.

The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1α was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.

Oxidative stress, progressive damage in the substantia nigra and plasma dopamine oxidation, in rats chronically exposed to ozone.

The purpose of our work was to determine the effects of oxidative stress on the neurodegeneration process in the substantia nigra, and to evaluate dopamine-oxidation metabolites in the plasma using a cyclic voltammetry (CV) technique. We have also studied the correlation between the increases in oxidized dopamine-species levels with the severity of lipid-peroxidation in the plasma. Sixty-four male Wistar rats were divided into four experimental groups and received air (Group I, control) or ozone (0.25 ppm) daily by inhalation for 4h for 15 (Group II), 30 (Group III), and 60 (Group IV) days. The brains were processed for immunohistochemical location of dopamine and p53 in the substantia nigra. Plasma collected from these animals was assayed for oxidized dopamine products using CV and lipid-peroxidation levels were measured. Our results indicate that chronic exposure to low O(3) doses causes that the number of dopaminergic neurons decreased, and p53-immunoreactive cells increases until 30 days; which was a function of the time of exposure to ozone. Oxidative stress produces a significant increase in the levels of the dopamine quinones (DAQs) that correlated well (r=0.962) with lipid peroxides in the plasma during the study period. These results suggest that DAQ could be a reliable, peripheral oxidative indicator of nigral dopaminergic damage in the brain.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Effects of testosterone and growth hormone on long-term retention and extinction of a passive avoidance response in young and aged rats.

Wistar rats were divided into two blocks: young and aged. Each block was then randomly divided into the following groups: (1) Control (saline solution), (2) Growth Hormone (GH), (3) Testosterone enanthate, and (4) GH plus testosterone enanthate. Animals were trained on a one-trial passive avoidance conditioning and tested for retention 24 h after training and thereafter twice a week until the extinction response occurred. Results showed that GH, testosterone, and GH plus testosterone improved long-term memory in young rats. Both GH and testosterone delayed the extinction process in young and aged rats. The GH-testosterone interaction delayed the extinction only in young rats.

Morphological recovery of the granule cells from the olfactory bulb after the cessation of acute ozone exposure.

The purpose of this study was to analyze the possible morphological recovery of the granule cells in the olfactory bulb as a consequence of oxidative stress after an acute ozone exposure. Rats were divided in two groups: Control (air exposed) and experimental group, exposed 4 h, to 1 ppm ozone and divided into 4 subgroups, which were sacrificed at 2 and 24 h, 10 and 15 days, respectively. Olfactory bulbs were processed with the rapid Golgi method and for transmission electron microscopy. The granule cells of the olfactory bulb disclosed less dendritic spine density at 2, 24 h, and 10 days after the exposure compared with controls. At 15 days, the number of spines increased to values similar to those found in controls. The granule cells ultrastructure demonstrated an increment in lipofucsin granules, as well as swollen organelles, changes that decreased overtime. This change decline might be related to a partial recovery of the associative granule cells function.

Effects of different ozone doses on memory, motor activity and lipid peroxidation levels, in rats.

Ozone is one of the main atmospheric pollutants. Its inhalation causes an increase in free radicals, when these free radicals are not compensated by antioxidants, it leads to an oxidative stress state. This oxidative stress state has been implicated in neurodegenerative processes. To determine the effects of oxidative stress caused by exposure to ozone on memory and motor activity, we used 120 male Wistar rats exposed to one of the following ozone doses, (0.0, 0.1, 0.4, 0.7, 1.1 and 1.5 ppm), for four hours. After ozone exposure, short and long term memory of a one trial passive avoidance test were measured, and motor activity was registered for five minutes, in 10 rats of each group. In 16 rats exposed to 0.0, 0.4, 0.7 or 1.1 ppm lipid peroxidation levels from frontal cortex, hippocampus, striatum and cerebellum, were measured. Results show that ozone, causes memory impairment from doses of 0.7 ppm, decrease in motor activity from doses of 1.1 ppm, and increase in lipid peroxidation levels from doses of 0.4 ppm. that increase with the dose.

Motor impairments in an oxidative stress model and its correlation with cytological changes on rat striatum and prefrontal cortex.

Exposure to ozone results in an increased production of free radicals which causes oxidative stress. The purpose of this study was to determine the effects of ozone exposure on motor behavior and its correlation with the cytology of the striatum and prefrontal cortex. Twenty-four male Wistar rats were exposed to 1 p.p.m. (parts per million) ozone for 4 hrs in a closed chamber. Control group was exposed to flowing air. Twenty-four hours after ozone exposure, the motor behavior was measured. After that, the animals were perfused and the brains were placed in Golgi stain. The analysis consisted in counting the dendritic spines in 5 secondary and 5 tertiary dendrites of each of the 20 medium size spiny neurons of striatum and 20 pyramidal neurons of prefrontal cortex analyzed. Our results showed alterations in motor behavior and a significant reduction of dendritic spines, and provided evidence that the deterioration in motor behavior is probably due to the reduction in spine density in the neurons of striatum and prefrontal cortex.

Taurine increases rat survival and reduces striatal damage caused by 3-nitropropionic acid.

Taurine acts as an antioxidant protecting neurons from free radical-mediated cellular damage. 3-nitropropionic acid (3-NP) inhibits energy metabolism, initiating oxidative stress. With the objective to examine whether taurine can protect glia and neurons from damage produced by 3-NP, male Wistar and Sprague-Dawley rats were treated with either (1) saline, (2) taurine (3) 3-NP and saline, or (4) 3-NP and taurine for 4 days. Survival was determined and brains were processed immunohistochemically. Large striatal lesions and increased GFAP, SOD, and taurine immunoreactivity were detected in the 3-NP group when compared with control groups. In contrast, animals receiving 3-NP and taurine exhibited less GFAP, SOD, and taurine immunoreactivity, along with increased survival rates. Results indicate that taurine treatment after 3-NP administration protects the striatum from damage.

Effects of taurine on ozone-induced memory deficits and lipid peroxidation levels in brains of young, mature, and old rats.

To determine the antioxidant effects of taurine on changes in memory and lipid peroxidation levels in brain caused by exposure to ozone, we carried out two experiments. In the first experiment, 150 rats were separated into three experimental blocks (young, mature, and old) with five groups each and received one of the following treatments: control, taurine, ozone, taurine before ozone, and taurine after ozone. Ozone exposure was 0.7-0.8 ppm for 4 h and taurine was administered ip at 43 mg/kg, after or before ozone exposure. Subsequently, rats were tested in passive avoidance conditioning. In the second experiment, samples from frontal cortex, hippocampus, striatum, and cerebellum were obtained from 60 rats (young and old), using the same treatments with 1 ppm ozone. Results show both an impairment in short-term and long-term memory with ozone and an improvement with taurine after ozone exposure, depending on age. In contrast to young rats, old rats showed peroxidation in all control groups and an improvement in memory with taurine. When taurine was applied before ozone, we found high peroxidation levels in the frontal cortex of old rats and the hippocampus of young rats; in the striatum, peroxidation caused by ozone was blocked when taurine was applied either before or after ozone exposure.