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Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02âM V2O5 1âh, 3/week for 6 months) groups (nâ=â10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.
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Enfermedad de Alzheimer , Encéfalo , Modelos Animales de Enfermedad , Memoria Espacial , Compuestos de Vanadio , Animales , Masculino , Administración por Inhalación , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/patología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/patología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Angiopatía Amiloide Cerebral/inducido químicamente , Angiopatía Amiloide Cerebral/patología , Espinas Dendríticas/efectos de los fármacos , Espinas Dendríticas/patología , Corteza Entorrinal/efectos de los fármacos , Corteza Entorrinal/patología , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/patología , Aprendizaje por Laberinto/efectos de los fármacos , Ovillos Neurofibrilares/efectos de los fármacos , Ovillos Neurofibrilares/patología , Placa Amiloide/inducido químicamente , Placa Amiloide/patología , Ratas Wistar , Memoria Espacial/efectos de los fármacos , Compuestos de Vanadio/administración & dosificación , Compuestos de Vanadio/toxicidadRESUMEN
Testosterone (T), estrogen receptor alpha (ERα), and androgen receptor (AR) play a significant role in the regulation of paternal behavior. We determined the effects of deprivation of paternal care on alterations in paternal behavior, T concentrations in plasma, and the presence of ERα and AR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB), as well as the corticosterone (CORT) concentrations in plasma caused by deprivation of paternal care in the Mongolian gerbil (Meriones unguiculatus). Twenty pairs of gerbils were formed; the pups were deprived of paternal care (DPC) in 10 pairs. In another 10 pairs, the pups received paternal care (PC). Ten males raised in DPC condition and 10 males raised in PC conditions were mated with virgin females. When they became fathers, each DPC male and PC male was subjected to tests of paternal behavior on day three postpartum. Blood samples were obtained to quantify T and CORT concentrations, and the brains were removed for ERα and AR immunohistochemistry analyses. DPC males gave less care to their pups than PC males, and they had significantly lower T concentrations and levels of ERα and AR in the mPOA and BNST than PC males. DPC males also had higher CORT concentrations than PC males. These results suggest that in the Mongolian gerbil father's absence causes a decrease in paternal care in the offspring, which is associated with alterations in the neuroendocrine mechanisms that regulate it.
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Receptores Androgénicos , Núcleos Septales , Animales , Femenino , Masculino , Humanos , Gerbillinae/fisiología , Receptores Androgénicos/metabolismo , Núcleos Septales/metabolismo , Receptor alfa de Estrógeno/metabolismo , Conducta Paterna/fisiología , Área Preóptica/metabolismo , Padre , CorticosteronaRESUMEN
Introducción: En años reciente se señalado que trastor-nos como la obesidad, la diabetes mellitus tipo 2 (DMT-II) es-tán asociados a deterioro cognitivo. Una posibilidad para com-prender la relación entre la cognición y estos trastornos sonlos biomarcadores en sangre. Objetivo: El objetivo de esta investigación fue determinarla relación de la hemoglobina glucosilada (HbA1c) y lípidoscon el desempeño cognitivo de pacientes que están expues-tos varios factores de riesgo vascular en comparación con pa-cientes que tienen menos factores de riesgo. Metodología: Se llevó a cabo un muestreo no probabilís-tico por conveniencia. Se consideraron a adultos de ambossexos que tuvieran una edad mayor a 18 años y que conta-ran con algún factor de riesgo como un estilo de vida seden-tario y/o diagnóstico de DMT-II, hipertensión u obesidad. Losparticipantes (n=28) fueron evaluados mediante EvaluaciónCognitiva Montreal (MoCA) y tareas para evaluar memoria detrabajo verbal y visoespacial (Dspan y Mspan). Asimismo, sedeterminaron los niveles de hemoglobina glicosilada (HbA1c),colesterol (HDL y LDL) y triglicéridos (TG). Resultados: Se encontró que los niveles elevados deHbA1c y TG se asociaron con una menor puntuación en laprueba MoCA, mientras que los niveles elevados de HDL seasociaron con mejor desempeño cognitivo en dicha prueba.Al dividir a la muestra en función de la cantidad de factoresde riesgo vascular a los que han sido expuestos se encon-tró que a mayor presencia de factores de riesgo la relaciónde la HbA1c y TG con un menor desempeño cognitivo esmás fuerte. Conclusión: Se concluye que la relación entre biomarca-dores y funciones cerebrales es fuerte y dependiente de lacantidad de factores de riesgo vascular a los que están ex-puestos los pacientes.(AU)
Introduction: In recent years it has been reported thatdisorders such as obesity and type 2 diabetes mellitus (T2DM)are associated with cognitive impairment. One possibility tounderstand the relationship between cognition and these dis-orders is blood biomarkers. Objective: The aim of this research was to determine therelationship of glycosylated hemoglobin (HbA1c) and lipidswith cognitive performance in patients who are exposed tovarious vascular risk factors compared with patients who havefewer risk factors. Methodology: Non-probability convenience sampling wasperformed. Adults of both sexes who were older than 18 years of age and who had some risk factor such as a sedentarylifestyle and/or diagnosis of T2DM, hypertension, or obesitywere considered. Participants (n=28) were assessed byMontreal Cognitive Assessment (MoCA) and tasks to evaluateverbal and visuospatial working memory (Dspan and Mspan).Glycosylated hemoglobin (HbA1c), cholesterol (HDL and LDL)and triglycerides (TG) levels were also determined. Results: It was found that elevated HbA1c and TG levelswere associated with a lower score on the MoCA test, whileelevated HDL levels were associated with better cognitive per-formance on the MoCA test. When the sample was divided ac-cording to the number of vascular risk factors to which theyhad been exposed, it was found that the greater the presenceof risk factors the stronger the relationship of HbA1c and TGwith poorer cognitive performance. Conclusion: We conclude that the relationship betweenbiomarkers and brain function is strong and dependent on thenumber of vascular risk factors to which patients are exposed.(AU)
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Humanos , Masculino , Femenino , Cognición , Biomarcadores , Lípidos , Obesidad , Diabetes Mellitus Tipo 2 , Ciencias de la Nutrición , Estilo de Vida , Glucosa , Nutrición, Alimentación y DietaRESUMEN
Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.
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Vanadium (V) toxicity depends on its oxidation state; it seems that vanadium pentoxide (V2O5) is the most toxic to the living cells. It has been reported that oral administration induces changes in motor activity and learning; in rats, I.P. administration increases lipid peroxidation levels in the cerebellum and the concentration of free radicals in the hippocampus and cerebellum. Mice that inhaled V2O5 presented a reduced number of tubulin+ in Leydig and Sertoli cells; it has also been reported that inhaled V2O5 induces loss of dendritic spines, necrosis, and hippocampus neuropil alterations; considering the direct consequence of the interaction of V with cytoskeletal components, makes us believe that V2O5 exposure could cause neuronal death in the hippocampus similar to that seen in Alzheimer disease. This work aimed to determine pyramidal hippocampal CA1 cytoskeletal alterations with Bielschowsky stain in rats exposed to V2O5. Male Wistar rats inhaled 0.02 M of V2O5 one h two times a week for two and six months. We found that rats, which inhaled V2O5 reached 56,57% of dead neurons after six months of inhalation; we recognize strong argyrophilic and collapsed somas and typical flame-shaped in all V-exposed rats hippocampus CA1 compared to controls. We also observe somatodendritic distortions. Axons and dendrites displayed thick dark bands replaced by noticeable thickening and nodosities and the cytoskeleton fibrillary proteins' linear traces. Our findings suggest that V2O5 inhalation induces Alzheimer-like cell death with evident cytoskeletal alterations.
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Lung cancer incidence and mortality have significantly increased in women worldwide. Lung adenocarcinoma is the most common form of lung cancer globally. This type of lung cancer shows differences by sex, including the mutational burden, behavior, clinical characteristics, and response to treatment. The effect of sex on lung cancer patients' survival is still controversial; however, lung adenocarcinoma is considered a different disease in women and men. Moreover, lung adenocarcinoma is strongly influenced by estrogen and is also different depending on the hormonal status of the patient. Young pre-menopausal women have been explored as an independent group. They presented in more advanced stages at diagnosis, exhibited more aggressive tumors, and showed poor survival compared to men and post-menopausal women, supporting the role of sex hormones in this pathology. Several reports indicate the estrogen's role in lung carcinogenesis and tumor progression. Thus, there are currently some clinical trials testing the efficacy of antihormonal therapy in lung cancer treatment. This mini review shows the updated data about lung cancer in women, its characteristics, the etiological factors that influence carcinogenesis, and the critical role of estrogen in lung cancer and treatment.
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Amoebae of the genus Acanthamoeba are etiological agents of granulomatous amoebic encephalitis (GAE). Recently, through an in vivo GAE model, Acanthamoeba trophozoites were immunolocalized in contact with the peripheral nervous system (PNS) cells-Schwann cells (SC). In this study, we analyzed in greater detail the in vitro early morphological events (1, 2, 3, and 4 h) during the interaction of A. culbertsoni trophozoites (ATCC 30171) with SC from Rattus norvegicus (ATCC CRL-2941). Samples were processed for scanning and transmission electron microscopy as well as confocal microscopy. After 1 h of interaction, amoebae were observed to be adhered to the SC cultures, emitting sucker-like structures associated with micro-phagocytic channels. In addition, evidence of necrosis was identified since edematous organelles as well as multivesicular and multilamellar bodies characteristics of autophagy were detected. At 2 h, trophozoites migrated beneath the SC culture in which necrosis and autophagy persisted. By 3 and 4 h, extensive lytic zones were observed. SC necrosis was confirmed by confocal microscopy. We reported for the first time the induction of autophagic and necrotic processes in PNS cells, associated in part with the contact-dependent pathogenic mechanisms of A. culbertsoni trophozoites.
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Synaptic plasticity is the process by which long-lasting changes take place at synaptic connections. The phenomenon itself is complex and can involve many levels of organization. Some authors separate forms into adaptations that have positive or negative consequences for the individual. It has been hypothesized that an increase in the number of synapses may represent a structural basis for the enduring expression of synaptic plasticity during some events that involve memory and learning; also, it has been suggested that perforated synapses increase in number after some diseases and experimental situations. The aim of this study was to analyze whether dopamine depletion induces changes in the synaptology of the corpus striatum of rats after the unilateral injection of 6-OHDA. The findings suggest that after the lesion, both contralateral and ipsilateral striata exhibit an increased length of the synaptic ending in ipsilateral (since third day) and contralateral striatum (since Day 20), loss of axospinous synapses in ipsilateral striatum and a significant increment in the number of perforated synapses, suggesting brain plasticity that might be deleterious for the spines, because this type of synaptic contacts are presumably excitatory, and in the absence of the modulatory effects of dopamine, the neuron could die through excitotoxic mechanisms. Thus, we can conclude that the presence of perforated synapses after striatal dopamine depletion might be a form of maladaptive synaptic plasticity.
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Cuerpo Estriado/ultraestructura , Dopamina/fisiología , Plasticidad Neuronal , Sinapsis/ultraestructura , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/fisiología , Dopamina/deficiencia , Masculino , Microscopía Electrónica , Plasticidad Neuronal/fisiología , Oxidopamina/farmacología , Ratas , Ratas Wistar , Sinapsis/efectos de los fármacos , Sinapsis/fisiologíaRESUMEN
Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 den-drites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of den-dritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines,it was found that its length considerably exceeded that reported in mammals, with dendritic spines upto 8 µm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution.
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Cuerpo Estriado/citología , Aparato de Golgi/ultraestructura , Neuronas/ultraestructura , Tortugas/anatomía & histología , Animales , Espinas Dendríticas/ultraestructuraRESUMEN
Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it has been reported that the overexposure causes neurotoxicity manifested as extrapyramidal symptoms similar to those observed in Parkinson disease (PD). Recently, our group reported that mice that inhaled for 5 months the mixture of manganese chloride (MnCl(2)) and manganese acetate Mn(OAc)(3) developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons, dopamine depletion and improved behavior with l-DOPA treatment. However, this model has only been characterized in mice. In order to have a well-supported and generalizable model in rodents, we used male Wistar rats that inhaled a mixture of 0.04 M MnCl(2) and 0.02 M Mn(OAc)(3), 1h three times a week for 6 months. Before Mn exposure, animals were trained to perform motor tests (Beam-walking and Single-pellet reaching tasks) and were evaluated each week after the exposure. The mixture of MnCl(2)/Mn(OAc)(3) caused alterations in the motor tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus Pallidus or striatum. With these results we conclude that the inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD.
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Modelos Animales de Enfermedad , Intoxicación por Manganeso/complicaciones , Enfermedad de Parkinson/etiología , Administración por Inhalación , Análisis de Varianza , Animales , Antiparkinsonianos/uso terapéutico , Encéfalo/metabolismo , Encéfalo/patología , Conducta Alimentaria/efectos de los fármacos , Levodopa/uso terapéutico , Locomoción/efectos de los fármacos , Masculino , Compuestos de Manganeso/administración & dosificación , Ratones , Actividad Motora/efectos de los fármacos , Examen Neurológico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Fosfopiruvato Hidratasa/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Tirosina 3-Monooxigenasa/metabolismo , Grabación en VideoRESUMEN
Lafora disease (LD) is an autosomal recessive, always fatal progressive myoclonus epilepsy with rapid cognitive and neurologic deterioration. One of the pathological hallmarks of LD is the presence of cytoplasmic PAS+polyglucosan inclusions called Lafora bodies (LBs). Current clinical and neuropathological views consider LBs to be the cause of neurological derangement of patients. A systematic study of the ontogeny and structural features of the LBs has not been done in the past. Therefore, we undertook a detailed microscopic analysis of the neuropile of a Laforin-deficient (epm2a-/-) mouse model. Wild type and epm2a-/- mice were sacrificed at different ages and their encephalon processed for light microscopy. Luxol-fast-blue, PAS, Bielschowski techniques, as well as immunocytochemistry (TUNEL, Caspase-3, Apaf-1, Cytochrome-C and Neurofilament L antibodies) were used. Young null mice (11 days old) showed necrotic neuronal death in the absence of LBs. Both cell death and LBs showed a progressive increment in size and number with age. Type I LBs emerged at two weeks of age and were distributed in somata and neurites. Type II LBs appeared around the second month of age and always showed a complex architecture and restricted to neuronal somata. Their number was considerably less than type I LBs. Bielschowski method showed neurofibrillary degeneration and senile-like plaques. These changes were more prominent in the hippocampus and ventral pons. Neurofibrillary tangles were already present in 11 days-old experimental animals, whereas senile-like plaques appeared around the third to fourth month of life. The encephalon of null mice was not uniformly affected: Diencephalic structures were spared, whereas cerebral cortex, basal ganglia, pons, hippocampus and cerebellum were notoriously affected. This uneven distribution was present even within the same structure, i.e., hippocampal sectors. Of special relevance, was the observation of the presence of immunoreactivity to neurofilament L on the external rim of type II LBs. Perhaps, type II LB is not the end point of a metabolic abnormality. Instead, we suggest that type II LB is a highly specialized structural and functional entity that emerges as a neuronal response to major carbohydrate metabolism impairment. Early necrotic cell death, neurocytoskeleton derangement, different structural and probably functional profiles for both forms of LBs, a potential relationship between the external rim of the LB type II and the cytoskeleton and an uneven distribution of these abnormalities indicate that LD is both a complex neurodegenerative disease and a glycogen metabolism disorder. Our findings are critical for future studies on disease mechanisms and therapies for LD. Interestingly, the neurodegenerative changes observed in this LD model can also be useful for understanding the process of dementia.
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Citoesqueleto/patología , Fosfatasas de Especificidad Dual/genética , Enfermedad de Lafora/genética , Enfermedad de Lafora/patología , Degeneración Nerviosa/patología , Neuronas/patología , Animales , Ganglios Basales/patología , Tronco Encefálico/patología , Citoplasma/patología , Modelos Animales de Enfermedad , Femenino , Hipocampo/patología , Enfermedad de Lafora/metabolismo , Masculino , Ratones , Ratones Mutantes , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Ovillos Neurofibrilares/patología , Neurópilo/patología , Fenotipo , Placa Amiloide/patología , Proteínas Tirosina Fosfatasas no Receptoras , Área Tegmental Ventral/patologíaRESUMEN
The present study examines the ability of melatonin to protect striatal dopaminergic loss induced by 6-OHDA in a rat model of Parkinson's disease, comparing the results with L-DOPA-treated rats. The drugs were administered orally daily for a month, their therapeutic or dyskinetic effects were assessed by means of abnormal involuntary movements (AIMs) and stepping ability. At the cellular level, the response was evaluated using tyrosine hydroxylase immunoreactivity and striatal ultrastructural changes to compare between L-DOPA-induced AIMs and Melatonin-treated rats. Our findings demonstrated that chronic oral administration of Melatonin improved the alterations caused by the neurotoxin 6-OHDA. Melatonin-treated animals perform better in the motor tasks and had no dyskinetic alterations compared to L-DOPA-treated group. At the cellular level, we found that Melatonin-treated rats showed more TH-positive neurons and their striatal ultrastructure was well preserved. Thus, Melatonin is a useful treatment to delay the cellular and behavioral alterations observed in Parkinson's disease.
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La dermatofilosis es una infección causada por una bacteria Gram positiva perteneciente al orden de los Actinomycetales, llamada Dermatophilus congolensis. Se presenta como una dermatosis de carácter agudo, subagudo o crónico que afecta preferentemente al ganado pero también a una amplia variedad de animales domésticos y salvajes y al hombre. Tiene distribución universal, pero con mayor prevalencia en climas húmedos, tropicales y subtropicales. Es considerada una zoonosis menor que puede causar grandes perjuicios económicos en la industria del ganado y el cuero. Se realiza una revisión del tema junto con la presentación de un caso clínico sumamente atípico.
Dermatophilosis is an acute, subacute or chronic skin disease affecting a wide range of species of animals and man. It is caused by a Gram (+) bacteria of the order of the Actinomycetales named Dermatophilus congolensis. Presenting as an acute, subacute or chronic dermatosis affecting primarily cattle, but a wide variety of domestic and wild animals, and humans, as well. It is distributed worldwide but more prevalent in the humid tropical and subtropic areas. It is essential to emphasize the importance of this disease in livestock industry and leather production. The disease is reviewed and an unusual case is reported.
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Humanos , Femenino , Persona de Mediana Edad , Actinomycetales , Piel/patología , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/epidemiología , Gentamicinas/uso terapéutico , Infecciones por Actinomycetales/microbiología , Pomadas/uso terapéuticoRESUMEN
This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5mg/kg L-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with L-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl(2)/Mn(OAc)(3) are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.
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Acetatos , Antiparkinsonianos/uso terapéutico , Cloruros , Modelos Animales de Enfermedad , Levodopa/uso terapéutico , Compuestos de Manganeso , Actividad Motora/efectos de los fármacos , Compuestos Organometálicos , Enfermedad de Parkinson/tratamiento farmacológico , Administración por Inhalación , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Masculino , Ratones , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatologíaRESUMEN
The present study examines the effects of divalent and trivalent Manganese (Mn(2+)/Mn(3+)) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whether L-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice a week for five months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By the end of Mn exposure, 10 mice were orally treated with 7.5 mg/kg L-DOPA. After 5 months of Mn mixture inhalation, striatal dopamine content decreased 71%, the SNc showed important reduction in the number of TH-immunopositive neurons, mice developed akinesia, postural instability, and action tremor; these motor alterations were reverted with L-DOPA treatment. Our data provide evidence that Mn(2+)/Mn(3+) mixture inhalation produces similar morphological, neurochemical, and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.
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Vanadium (V) is a transition metal emitted to the atmosphere during the combustion of fossil fuels. Its current status as an atmospheric pollutant increases the need for information about the effects that this element might have on the reproductive health of exposed populations. The present study investigated changes in testicular ultrastructure following inhalation exposure of male mice to V (as vanadium pentoxide). Tissue V level was constant during the 12-week time period. We observed necrosis of spermatogonium, spermatocytes and Sertoli cells, as well as pseudo-nuclear inclusion and disruption of cellular junctions. Our findings stressed the importance of the hemato-testicular barrier in supporting the function of Sertoli cells and suggest as a possible target of V, tight junction proteins. Further analysis is needed in order to identify the role that reactive oxidative species (ROS) might have on these cellular junctions, and if a specific protein is the target of its toxic effects. The relevance of this report concerns the impact that metal air pollution could have on male fertility in dense cities with vehicular traffic problems.
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Contaminantes Atmosféricos/toxicidad , Exposición por Inhalación , Testículo/efectos de los fármacos , Testículo/ultraestructura , Compuestos de Vanadio/toxicidad , Contaminantes Atmosféricos/metabolismo , Animales , Núcleo Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Infertilidad Masculina/inducido químicamente , Masculino , Ratones , Microscopía Electrónica , Necrosis , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/ultraestructura , Células de Sertoli/efectos de los fármacos , Células de Sertoli/ultraestructura , Espermatocitos/efectos de los fármacos , Espermatocitos/ultraestructura , Espermatogonias/efectos de los fármacos , Espermatogonias/ultraestructura , Testículo/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/ultraestructura , Factores de Tiempo , Compuestos de Vanadio/metabolismoRESUMEN
Spatial memory may be severely impaired as a consequence of ageing and neurodegenerative diseases, conditions that include neuronal damage. Vanadium (V) is a metalloid widely distributed in the environment and exerts severe toxic effects on a wide variety of biological systems. Reports about V inhalation toxicity on the CNS are limited, thus the purpose of this study is to determine the effects of Vanadium pentoxide (V(2)O(5)) inhalation (0.02M) on the memory and its correlation with the cytology of the hippocampus CA1. Forty eight CD-1 male mice were trained in spatial memory tasks and inhaled 1h twice a week; after each inhalation animals were evaluated and sacrificed from 1 to 4 weeks, perfused and processed for Golgi method and for ultrastructure evaluation. The cytological analysis consisted in counting the number of dendritic spines of 20 pyramidal neurons of hippocampus CA1, as well as ultrastructural characteristics. Results show that V inhalation produces a time dependent loss of dendritic spines, necrotic-like cell death, and notorious alterations of the hippocampus CA1 neuropile, which correlate with spatial memory impairment. Our data suggest that V induces important cellular and functional alterations, fact that deserves special attention since the concentration's trend of this element in the atmosphere is increasing.