RESUMO
Erythropoietin in the nervous system is a potential neuroprotective factor for cerebral ischemic damage due to specific-binding to the erythropoietin receptor, which is associated with survival mechanisms. However, the role of its receptor is unclear. Thus, this work assessed whether a low dose (500UI/Kg) of intranasal recombinant human erythropoietin administered 3h after ischemia induced changes in the activation of its receptor at the Tyr456-phosphorylated site in ischemic hippocampi in rats. The results showed that recombinant human erythropoietin after injury maintained cell survival and was associated with an increase in receptor phosphorylation at the Tyr456 site as an initial signaling step, which correlated with a neuroprotective effect.
Assuntos
Isquemia Encefálica/metabolismo , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Hipocampo/efeitos dos fármacos , Receptores da Eritropoetina/metabolismo , Administração Intranasal , Animais , Isquemia Encefálica/patologia , Sobrevivência Celular/efeitos dos fármacos , Citoproteção , Eritropoetina/administração & dosagem , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Fosforilação , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Tirosina/metabolismoRESUMO
Overactivation of NMDA-Rs may mediate excitotoxic cell death associated with epileptic seizures, and hypoxic-ischemic conditions. We assessed whether repeated subcutaneous administration of l-glutamate to neonatal rats affects the subunit composition of NMDA-Rs. Accordingly, cortical and hippocampal tissue from 14-day-old rats was analyzed by Western blotting and RT-PCR to quantify the protein and mRNA expression of different NMDA-R subunits. In addition, tissue sections were Nissl stained to assess the cell damage in this tissue. Early exposure of neonatal rats to L-glutamate differentially affects the expression of mRNA transcripts for NMDA-R subunits in the cerebral cortex and hippocampus. In the cerebral cortex, a decrease in NR2B subunit mRNA expression was observed, as well as a loss of NR1 and NR2A protein. By contrast, neonatal L-glutamate administration augmented the transcripts encoding the NR1, NR2B, and NR2C subunits in the hippocampal formation. The expression of mRNA encoding the NR2A subunit was not affected by neonatal L-glutamate administration in either of the brain regions examined. This differential expression of NMDA-R subunits following neonatal exposure to L-glutamate may represent an adaptive response of the glutamate receptors to overactivation in order to reduce the effect of high L-glutamate during the early period of life when the animal is more vulnerable to excitotoxicity.
Assuntos
Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Neurotoxinas/toxicidade , Receptores de N-Metil-D-Aspartato/metabolismo , Análise de Variância , Animais , Western Blotting , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIMS: The article highlights the general structural characteristics, functional properties and distribution of glutamate transporters, as well as the role they play in epilepsy and oxidative stress. DEVELOPMENT: Transporters of amino acids such as glutamate are considered to be proteins that are extremely important in the central nervous system because they participate in the capture of the neurotransmitter following its release in the synaptic cleft, thus putting an end to its effect and limiting glutamate-mediated excitability. These proteins belong to the family of Na+/K+ dependent transporters. A growing body of evidence has been gathered to show that these transporters are involved in several neuronal disorders, such as epilepsy and cerebral ischaemia. In this regard, it is considered that some defect in the structure of the transporters could affect their functioning and, therefore, favour the hyperexcitability produced by glutamate; this in turn would lead to the pathological disorders that are found in epilepsy. CONCLUSIONS: A detailed study of the structure and functioning of these transporters, as well as the role they play in the more common neurological diseases, such as epilepsy, would afford us a clearer view of new therapeutic alternatives with which to fight this kind of neuronal disorder in the future.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/química , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Epilepsia/metabolismo , Ácido Glutâmico/metabolismo , Estresse Oxidativo , Sistema X-AG de Transporte de Aminoácidos/genética , Animais , Transporte Biológico/fisiologia , Epilepsia/genética , Humanos , Modelos Moleculares , Estrutura MolecularRESUMO
The ultrastructure of the Atlantic Bottlenose dolphin Harderian gland (HG) has been described but some questions remain unanswered. The purpose of this work was to define the gland's structure, ultrastructure and the differences between cells (types I and II) of the male dolphin using optic, fluorescence and electron transmission microscopy. Three different cells were observed under optic and fluorescence microscopic examination, while only two cell types (types I and II) were distinguished by electron transmission microscopy. Type I (oval nuclear envelope) exhibited three different cell populations and type II (indented nuclear envelope) exhibited two different cell populations. Although, we observed both types of vesicles in both types of cells they differed, principally, in quantity. The glands also possessed prominent duct systems, with three orders of complexity. The dolphin orbital HG appears to function as a mixed heterologous gland with two types of cells that exhibit both types of vesicles and other distinguishable differences.
Assuntos
Golfinho Nariz-de-Garrafa/anatomia & histologia , Glândula de Harder , Animais , Glândula de Harder/anatomia & histologia , Glândula de Harder/citologia , Glândula de Harder/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão/veterinária , Microscopia de Fluorescência/veterináriaRESUMO
Experimental paradigms conducted to assess the neurotoxic effects of ethanol exposure on hippocampus development have yielded controversial findings. Hippocampal CA1 population and some cytoarchitectural parameters of pyramidal cells were studied after exposure to ethanol during early development, in rats. Examination of 30-day-old offspring of rats exposed to moderate levels of ethanol during gestation through lactation showed an increased volume of the hippocampal CA1 field compared to untreated or pair-fed control pups, as well as a reduced number of pyramidal neurons. In addition, the number of spines from surviving CA1 pyramidal neurons was reduced. Furthermore, stubby and wide spines were proportionally increased, while the proportion of mushroom and ramified spines was reduced; no variation in the proportion of thin spines was observed. Because alcoholic women usually drink alcohol before, during, and after pregnancy, a broad-range experimental model of alcohol exposure was used in this study. The present findings show that experimental exposure to moderate levels of ethanol, resembling the human situation in alcoholic mothers, leads to loss of hippocampal CA1 pyramidal neurons, along with several pathological and plastic events in the dendritic arborization of these neurons. Some ethanol-induced excitotoxicity-related mechanisms, which may be underlying these effects, are discussed.
Assuntos
Animais Recém-Nascidos/fisiologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Hipocampo/patologia , Animais , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Feminino , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , SobrevidaRESUMO
AIMS: This work analyses the main studies dealing with the mechanisms by which the brain is altered by chronic stress and the impact of social stimuli on the activation of these mechanisms, which can lead to behavioural disorders and cognitive impairment in communities of mammals. DEVELOPMENT: The physiological and hormonal responses triggered as a response to stress are linked to alterations in certain areas of the brain and more particularly in the hippocampus. These mechanisms include hyperactivity of the hypothalamus-pituitary-adrenal axis, raised levels of corticosteroids and excitatory amino acids, neurotoxicity due to intracellular accumulation of calcium, apoptosis and a number of factors having to do with the immunological system. Most of these studies have involved the exogenous application of supraphysiological levels of corticosteroids or challenging the individual with stimuli that do not properly belong to their natural surroundings. Nevertheless, it is also possible that these mechanisms are triggered by aversive social stimuli from the natural environment, such as confrontation, establishing hierarchies, neglect and social evaluation. It has been proved that social stress has important effects on conduct and health, especially with regard to the structural and functional integrity of the brain. CONCLUSIONS: Social stress can trigger important alterations in the nervous system of individuals exposed to it and these changes can manifest themselves as varying types of disorders affecting conduct and the cognitive skills. Nevertheless, not all natural surroundings give rise to these adverse effects, as balanced communities offer their members support, protection and a series of other advantages.
Assuntos
Encéfalo/fisiologia , Meio Social , Estresse Psicológico/fisiopatologia , Corticosteroides/metabolismo , Animais , Sintomas Comportamentais/fisiopatologia , Encéfalo/anatomia & histologia , Transtornos Cognitivos/fisiopatologia , Feto/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologiaRESUMO
The presence of a cortex and medulla in the superficial pineal gland has been a controversial point in the morphology of this structure in mammals. The published reports indicate contradictory data especially in rodents. In this study the pineal gland of 15-day-old male rats (Rattus norvegicus) were studied, using scanning electron microscopy, in an attempt to determine whether or not a cortex and medulla are apparent in the pineal gland of young rats. The superficial pineal gland of the 15-day-old rat exhibited both a cortex and a medulla; these areas exhibited different structural organizations. The cortex had a thickness of 40-80 microm and the cells did not show a particular arrangement. The center of the gland was composed of a medulla, which had a width of 1000-1200 microm, and consisted of cells arranged in cords; its morphology was distinctly different from that of the cortex.
Assuntos
Glândula Pineal/ultraestrutura , Ratos Sprague-Dawley/anatomia & histologia , Animais , Animais Recém-Nascidos/anatomia & histologia , Feminino , Masculino , Microscopia Eletrônica de Varredura/veterinária , RatosRESUMO
Early overstimulation of ionotropic glutamate receptors (iGluRs), such as the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, produces excitotoxicity in several brain regions. The molecular composition of those receptors and their regulation by intracellular signaling systems could be determinants in the development of progressive neurodegenerative mechanisms in the central nervous system (CNS). Studies of p38 mitogen-activated protein kinase (MAPK) activation, morphologic changes including cell number, and the expression of the NR1 and GluR2 subunits, by reverse transcriptase-PCR were evaluated at early postnatal ages (postnatal day [PD]8-14) in cerebral cortex of rats treated with monosodium glutamate (MSG; 4 mg/g body weight) administered subcutaneously on PD1, 3, 5, and 7. An important increase in p38 activity at PD8 and loss of cortical cell number were observed from PD8-14 in animals treated with MSG, together with significant morphologic changes characterized by cell shrinkage, nuclear hyperchromatism, and cytoplasmic vacuolation. These morphologic changes were prevented by SB203580, an inhibitor of p38 signaling, at PD8-14. No change in cerebral cortex thickness was observed among experimental or control rats. A significant increase in NR1 subunit expression was observed in response to MSG from PD8-14. GluR2 expression increased from PD8-12, but at PD14, its expression was reduced to 54% with respect to controls. SB203580 prevented alone the decreased in GluR2 expression induced by MSG. These results suggest that initial neuronal death (at PD8 and 10) in cerebral cortex may be due to an excessive Ca2+ influx through NMDA receptors, whereas the further damage process could be mediated by AMPA receptors through p38 signaling. This could represent a determinant mechanism to decide whether nerve cells survive or die.
Assuntos
Morte Celular/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Neurônios/efeitos dos fármacos , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Fator 2 Ativador da Transcrição , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Proteínas de Transporte , Sobrevivência Celular , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Densitometria/métodos , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Imidazóis/farmacologia , Marcação In Situ das Extremidades Cortadas/métodos , Masculino , Proteínas Mitocondriais , Neurônios/citologia , Neurônios/metabolismo , Gravidez , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Piridinas/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Receptores de AMPA/genética , Receptores de N-Metil-D-Aspartato/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The objective of this work was to describe the anatomy of placentas from women who were at risk of exposure to parathion during their pregnancy, when examined with the light and scanning electron microscopes. Twenty term placentas were analyzed; 10 from women living in an agricultural area, who were at risk of exposure to parathion during their pregnancy, and 10 from women living in an urban area, not expressly exposed to pesticides. Each sample was examined with both light and scanning electron microscopes. Cholinesterase activity was significantly reduced in blood from women of the exposed group. In some placentas of women exposed to parathion, recent microinfarctions, microcalcifications and increased deposition of fibrinoid material were seen, along with a larger proportion of atypical characteristics of villi, such as bullous and balloon-like formations with nonhomogeneous surface, and other areas devoid of microvilli. These observations suggest that in chronic exposure to pesticides, the rate of atypical characteristics of placental villi increases, which could be related to changes in the fetus biology. In this study, one newborn from the exposed group showed intrauterine growth retardation and another one, some signs of hypoxia.
Assuntos
Inibidores da Colinesterase/efeitos adversos , Vilosidades Coriônicas/ultraestrutura , Microscopia Eletrônica de Varredura , Paration/efeitos adversos , Placenta/ultraestrutura , Adulto , Vilosidades Coriônicas/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Inseticidas/efeitos adversos , México , Placenta/efeitos dos fármacos , Gravidez , Resultado da GravidezRESUMO
The purpose of this study was to compare the natural fluorescence in the Harderian glands of the Syrian hamster, rat, mouse, Mongolian gerbil and guinea pig (both sexes). For each species, 10 animals (five males and five females) were used. Histological autofluorescence studies were performed using a fluorescence microscope (450-490 nm filter). Two different types of fluorescent cells were observed in both hamster (type AFI high intensity and type AFII, low fluorescence) and rat (type AFI, low fluorescence and type AFII, high fluorescence) Harderian glands. The fluorescence was basally located in all mice cells, whereas it was observed near the epithelial cell nuclei in the Mongolian gerbil (occupying two-thirds and one-third of the cells in males and females, respectively). A high intensity of fluorescence was present throughout the acinar cells in the guinea pig. The patterns of fluorescence identified exhibited a sexual dimorphism in all species studied. These results demonstrate that the Harderian glands of the animal species examined exhibit a variety of histological autofluorescence patterns.
Assuntos
Gerbillinae/anatomia & histologia , Cobaias/anatomia & histologia , Glândula de Harder/anatomia & histologia , Mesocricetus/anatomia & histologia , Camundongos Endogâmicos BALB C/anatomia & histologia , Ratos Wistar/anatomia & histologia , Animais , Cricetinae , Feminino , Fluorescência , Glândula de Harder/citologia , Glândula de Harder/ultraestrutura , Masculino , Camundongos , Microscopia de Fluorescência , RatosRESUMO
The N-methyl-D-aspartate receptor (NMDA-R) is fully functional in the rat early in embryogenesis, and diverse neuronal plasticity events are regulated through its activation later in postnatal development. On the other hand, systemic administration of glutamate (Glu) to rats at birth induces neuronal degeneration in glutamatergic central nervous system regions via Glu receptor activation. However, it is not known whether an increase in neonatal Glu levels modifies the gene expression of NMDA-R subunits, or if these putative changes are related to gamma-aminobutyric acid-mediated (GABAergic) neurotransmission. We measured, by means of semi-quantitative reverse transcriptase polymerase chain reaction, changes in gene expression of the NMDA-R subunits: NMDA-R1, NMDA-R 2A and NMDA-R 2B in cerebral cortex (CC), striatum (ST) and hippocampus (HP) in the brains of rats treated neonatally with monosodium L-glutamate (MSG). These studies were supported by histological and quantitative analysis of the glia. Our results showed histological evidence of neuronal damage, and increased glial cell number and activity were detected. This was seen mainly in the ST and HP of MSG-treated animals. Significant increases in NMDA-R1, 2A and 2B subunits gene expression was also observed in ST and HP but not in CC, where only NMDA-R 2B was increased in MSG-treated rats. Our data suggest that increases in Glu levels and activation of Glu-receptors after neonatal administration of MSG induce an increase in glial cell reactivity and important changes in NMDA-R molecular composition, with signs of neuronal damage.
Assuntos
Encéfalo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Receptores de N-Metil-D-Aspartato/genética , Animais , Animais Recém-Nascidos , Sequência de Bases , Encéfalo/metabolismo , Primers do DNA , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Gravidez , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The release of gonadotrophic hormones starts at puberty and, along with the subsequent estral cyclicity, is subject to hormonal feedback systems and to the action of diverse neuroactive substances such as gamma amino butyric acid and catecholamines. This study shows the effect of the administration during 40 days of protein-restricted and corn-based (tryptophan- and lysine-deficient) diets on the serotonin concentration in medial hypothalamic fragments as well as in follicle-stimulating luteinizing hormones, 17-beta-estradiol and progesterone serum levels, and estral cyclicity in 60- and 100-day-old rats (young, mature, and in gestation). In young rats, a delay in vaginal aperture development, and a lengthening of the estral cycle to a continuous anestral state was observed, mainly in the group fed corn. This group showed a 25% decrease in the serotonin concentration compared with the protein-restricted group, which exhibited an increase of 9% over the control group. Luteinizing hormone levels decreased in 16% and 13%, whereas follicle-stimulating hormone increased in 13% and 5% in the young animals of restricted groups, respectively, compared with the control group. Serum progesterone levels decreased only in young restricted versus control animals, and no differences were seen among adult and gestational rats. Serum levels of 17-beta-estradiol in restricted animals showed different concentration patterns, mainly in the corn group, which was higher at the 20th gestational day, falling drastically postpartum. The results obtained in this study show serotonin to be a very important factor in the release of gonadotrophic hormones and the start of puberty.
RESUMO
OBJECTIVE: To assess the genotoxic activity of N-nitroso diethylamine (NDEA), maleic hydrazide (MH), and ethyl methane sulfonate (EMS) using two systems: the comet assay on nuclei from Tradescantia, and the pink mutation test on Tradescantia staminal hairs (clone 4430). MATERIAL AND METHODS: Tradescantia cups was obtained from Laboratorio de Citogenética y Mutagénesis del Centro de Ciencias de la Atmósfera de la Universidad Nacional Autónoma de México and treated with: N-nitroso diethylamine (NDEA) at 1, 5, 10 mM, maleic hydrazide (MH) at 1, 5, 10 mM and ethyl methane sulfonate (EMS) at 15, 30 and 45 mM; and used in both pink mutation assay and comet assay using cellular nuclei from Tradescantia staminal hairs. The observation of staminal hair was realized along eight days (6-14) after treatment), flowers produced day 14 after treatment were utilized done according to Underbrink. In previous reports on plants, were comet assay was used, breaking cellular wall and separating by centrifugation gradient are necessary. Here, nuclei from staminal hairs were obtained by squashing the cells (is not necessary to utilize to break special procedure cellular wall), collected using a nylon mesh of 80 Mm and next the comet assay was applied. Student's T test was the statistical test used for analyzing the comet assay data. RESULTS: Both assays showed a great sensitivity to the studied mutagens. A relationship between the dose-pink event and the dose-tail length was evident. Even though the Tradescantia mutation assay is a sensitive test with MH and EMS, low doses of NDEA were not able to induce a significant increase in the pink event frequencies; however, the comet assay was able to detect the mutagenic effect of NDEA at the same dose. Thus, it is clear that the comet assay is highly sensitive to the lowest dose of chemical mutagens. CONCLUSIONS: The comet assay on nuclei from Tradescantia staminal hairs is a useful tool to monitor genotoxic agents; it is simple, highly sensitive, and faster than the pink mutation test.
Assuntos
Dietilnitrosamina/toxicidade , Metanossulfonato de Etila/toxicidade , Hidrazida Maleica/toxicidade , Testes de Mutagenicidade , Ensaio Cometa , Humanos , Mutação , Plantas/efeitos dos fármacos , Plantas/genéticaRESUMO
The prefrontal cortex activity is involved in organizing the short-term memory. Although the involvement of serotonin for an appropriate performance in learning and memory tests is well known, its role is still unclear; as is the cellular basis of short-term memory behavioral performance. Sprague-Dawley rats were stereotactically injected with 1 microg/microl of 5, 7-dihydroxitryptamine to cause a lesion to the dorsal raphe nucleus. Sham-operated or intact rats were also studied as control groups. Before surgery and 20 days post-operatively, each animal was placed in the Biel maze for five consecutive trials. In the pre-treatment test, all three groups decreased significantly the number of errors beginning with the fourth trial. The same occurred in the post-treatment test, except for the experimental group, whose animals committed less errors beginning with the second trial. After behavioral testing, the dorsomedial prefrontal cerebral cortex was dissected out, and the Golgi study of the third-layer pyramidal neurons revealed that the length of both the apical and the basilar dendrites was smaller than that of controls, and that the apical and oblique dendrites had a greater spine density. A major proportion of thin spines was also seen on the basilar and oblique dendrites, and more stubby spines were seen on the apical dendrite. Serotonin depletion in the prefrontal cerebral cortex resulted in cytoarchitectural alterations of the prefrontocortical pyramidal neurons, which may be underlying partially the greater efficiency observed in the short-term memory behavioral performance.
Assuntos
Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/metabolismo , Células Piramidais/fisiologia , Serotonina/metabolismo , Animais , Comportamento Animal/fisiologia , Dendritos/fisiologia , Dissecação , Feminino , Aprendizagem em Labirinto/fisiologia , Plasticidade Neuronal , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/cirurgia , Células Piramidais/citologia , Núcleos da Rafe/efeitos dos fármacos , Núcleos da Rafe/patologia , Núcleos da Rafe/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To determine whether occupational exposure of men to hydrocarbons has adverse effects on the quality of their semen. DESIGN: Comparative study. SETTING: The rubber industry in Mexico City. PATIENT(S): Forty-eight workers who were exposed to hydrocarbons for 2-24 years and 42 unexposed workers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Environmental hydrocarbon concentrations were determined by continuous air monitoring in all areas of the factory. Analyses of semen samples were performed in accordance with World Health Organization criteria. RESULT(S): Hydrocarbon concentrations were as follows: ethylbenzene, 220.7-234 mg/m3; benzene, 31.9-47.8 mg/m3; toluene, 189.7-212.5 mg/m3; and xylene, 47-56.4 mg/m3. The number of subjects with ejaculates that had normal characteristics was greater in the unexposed group (76%) than in the exposed group (17%). More abnormal characteristics were found in the semen of exposed workers than unexposed workers, including alterations in viscosity, liquefaction capacity, sperm count, sperm motility, and the proportion of sperm with normal morphology. Some abnormal characteristics correlated with the number of years of exposure to the hydrocarbons. CONCLUSION(S): Damage to the spermatogenic process resulting from hydrocarbon exposure was demonstrated by an increased rate of abnormalities in the semen of exposed workers compared with unexposed workers. This information may be useful for conducting future analyses of reproductive risks related to exposure to high concentrations of hydrocarbons.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Hidrocarbonetos/toxicidade , Exposição Ocupacional , Sêmen/efeitos dos fármacos , Sêmen/fisiologia , Adulto , Consumo de Bebidas Alcoólicas , Sobrevivência Celular/efeitos dos fármacos , Nível de Saúde , Humanos , Masculino , México/epidemiologia , Oligospermia/epidemiologia , Fumar , Aglutinação Espermática/efeitos dos fármacos , Contagem de Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacosRESUMO
Melatonin is a free radical scavenger and antioxidant. This indol is reported to efficiently scavenge both hydroxyl and peroxyl radicals and it also reduces both in vitro and in vivo tissue damage due to oxidants which generate oxygen toxic radicals. Lipopolysaccharide (LPS) administration induces oxidative damage in various tissues mainly due to its ability to increase reactive oxygen species. In the present work, we studied the morphological changes and lipid peroxidation in the Harderian gland after LPS administration and the effects of melatonin in preventing the induced changes. Hyperchromasia, vesicular degeneration, necrosis and infiltration with macrophages, monocytes and neutrophils were observed in the LPS-treated group (10 mg/kg, intraperitonally [i.p.]). Also, a typical structure of the glandular acini of the gland exhibited diffuse damage. In the LPS rats treated with melatonin (10 mg/kg, i.p.), a diminished number of infiltrative cells was seen, and cloudy swelling was reduced, as was nuclear hyperchromasia. Neither necrosis nor vesicular degeneration were noted in the melatonin-treated rats, and in general, glandular structure was preserved. Lipid peroxidation products increased significantly within six hours after LPS administration, and melatonin treatment decreased the LPS-dependent lipid peroxidation products. These data together suggest that melatonin protects the Harderian gland against LPS toxicity in terms of morphological damage.
Assuntos
Glândula de Harder/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Melatonina/farmacologia , Animais , Glândula de Harder/metabolismo , Glândula de Harder/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Monosodium L-glutamate (MSG) causes neuronal lesions in certain brain regions when systemically given to young animals. Also, when glutamate (Glu) builds up in the intersynaptic space, it induces neuroexcitatory and neurocytotoxic effects, events mediated by several Glu receptors. Some of these receptors such as NMDA and AMPA receptors are present in the very earliest developmental stages of the central nervous system and play a major role in neuronal plasticity during synaptogenesis. In this paper, the GABAergic system vulnerability was determined in terms of [3H]-GABA release during postnatal development. [3H]-GABA release on days 14, 21, 30, and 60 days after birth was assessed for the cerebral cortex (CC), hippocampus (Hp) and striatum (S) in rats perinatally treated at days 1, 3, 5, and 7 after birth with MSG. The results show a major decrease in baseline [3H]-GABA release in the CC (30 and 60 days after birth) and the Hp (beginning day 21 after birth) vs the control groups [intact rats and rats given a NaCl solution equimolar to that of MSG (eqNaCl)] while in the S baseline release remained unchanged. Stimulated [3H]-GABA release was decreased in the CC on days 14 and 21 after birth and significantly increased on day 60 after birth vs the controls. In the Hp, a decrease was seen on days 14, 21, and 60 after birth vs the controls while stimulated [3H]-GABA release was decreased in the S vs the controls at all ages studied. No significant differences in stimulated [3H]-GABA release were found between the intact group and the group treated with eqNaCl on days 30 and 60 after birth. Results show that CC, Hp and S GABAergic neurones are a major target for the effect of perinatally given MSG and suggest a possible decrease in the number of Hp GABAergic neurones while these results in CC and S suggest a modified neuronal plasticity. NMDA receptor and calcium involvement are discussed as significant mediators of these events.
Assuntos
Envelhecimento , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Glutamato de Sódio/farmacologia , Ácido gama-Aminobutírico/metabolismo , Animais , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Hipocampo/metabolismo , Ratos , Ratos Wistar , Cloreto de Sódio/farmacologia , TrítioRESUMO
The CA1 hippocampal region is involved in organizing several neuropsychological processes. Pyramidal cell dendritic spines in the CA1 field of rats subjected to chronic tryptophan diet restriction were quantified at 21, 40, and 60 days of age. At 40 days of age, the number of spines in the distal third of the apical dendrite was smaller in experimental animais. The same was true for the medial third of the apical dendrite and the basal dendrite at 60 days of age. The results could be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the hippocampal Ammon's horn and, particularly, on the CA1 pyramidal neurons as well as on aferences to the hippocampus. Since the present is a model of generalized tryptophan restriction, neurochemical studies are needed to dilucidate this hypothesis.
RESUMO
Glutamate, as a monosodium salt (MSG) has neurotoxic effects on some brain regions when systemically given to young rats. Few studies have been conducted to establish the mechanisms involved in studying neurotoxicity resulting in neuronal death by glutamate (Glu) and its effects as related to different brain neuropathologies under in-vivo conditions and where the cholinergic system shows vulnerability. Thus, this paper aims to evaluate the binding kinetics of quinuclynidyl benzylate (QNB) to muscarinic receptors for acetylcholine and the activity of choline acetyltransferase (CAT) in rats treated with MSG (4 mg/g on days 1, 3, 5, and 7 after birth) during the rat development stages (days 14, 21, 30, and 60) in different brain regions. The results show that perinatal treatment with MSG significantly decreases the CAT activity and increases the affinity of [3H]-QNB and the number of receptors of the brain cortex during the ages studied. The striatum showed increased CAT activity and BMAX on days 30 and 60 after birth. Affinity and the number of receptors increased in the hippocampus only between days 21 through 60 after birth. NaCl given at MSG equimolar doses only modified the CAT activity but had no effect on the [3H]-QNB binding kinetics in any of the regions studied. The results show that MSG alters cholinergic neurotransmission in the central nervous system (CNS) and induces the development of compensating events suggesting an involvement in neuronal plasticity during the development of rat CNS.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Fibras Colinérgicas/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Animais Recém-Nascidos/fisiologia , Encéfalo/fisiologia , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/crescimento & desenvolvimento , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/crescimento & desenvolvimento , Ácido Glutâmico/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Injeções Subcutâneas , Ratos , Ratos WistarRESUMO
Spontaneous [3H]dopamine ([3H]DA) overflow was measured from striatal slices in the presence of different glutamate (Glu) receptor agonists such as N-methyl-D-aspartate (NMDA), kainate (KA) and quisqualate (QA) and their corresponding antagonists, Dizocilpine maleate (MK-801), D-gamma-glutamyl-aminomethanesulfonic acid (GAMS) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. [3H]DA uptake and release in the presence of L-Arginine (L-Arg) and NG-nitro-arginine (L-N-Arg), an inhibitor of nitric oxide (NO) synthesis were also evaluated. L-N-Arg alone or combined with L-Arg significantly reduced [3H]DA uptake at 10 and 100 microM from 33% to 44% from striatal slices. Whereas, in brain synaptosomal fractions L-Arg induced a biphasic effect on that [3H]DA uptake in a dose dependent manner, and L-N-Arg showed an absolute inhibition in 80-90% of this [3H]DA uptake at 1-500 microM. The amino acids, lysine, valine and histidine (100 microM) had a little effect inhibitory on [3H]DA uptake from synaptosomal fractions. Glu agonists, NMDA (10 microM) and KA (10 microM) importantly increased the spontaneous [3H]DA overflow, which was blocked by MK-801 (10 microM) and GAMS (10 microM), respectively. QA had no effect on [3H]DA release. L-Arg (10-200 microM) potentiated the spontaneous [3H]DA overflow in a dose dependent fashion from striatal slices, being reverted by 10 microM L-N-Arg alone or in combination with all other compounds; whereas, lysine, histidine and valine did not modify that spontaneous [3H]DA overflow. Results support the hypothesis related to the participation of NO on DA transport possibly synthesized at the dopaminergic (DAergic) terminals in the striatum; also that L-Arg concentration may determine alternative mechanisms to regulate the DAergic activity at the striatum.