Vanadium inhalation in a mouse model for the understanding of air-suspended particle systemic repercussion.

There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature.

Toxic effects of inhaled manganese on the olfactory bulb: an ultrastructural approach in mice.

Olfactory dysfunction is a common symptom reported by patients with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Despite the knowledge gathered about the pathology of these diseases, little information has been generated regarding the ultrastructure modifications of the granule cells that regulate the information for odor identification. Swollen organelles and nuclear invaginations identified the exposed mice. Necrosis was evidenced at 4th week of exposure, whereas apoptosis arose at 8th week of exposure. A ruffled electron-dense membrane changes were also found. The changes observed could be explained by the reactive oxygen species generated by manganese and its effects on the membrane's structure and on the cytoskeleton's function. This study contributes to correlate metal air pollution and neurodegenerative changes with olfactory affection.

Inhalation of divalent and trivalent manganese mixture induces a Parkinson's disease model: immunocytochemical and behavioral evidences.

The present study investigates 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 cell death in the substantia nigra compacta (SNc) and correlating these alterations with motor disturbances. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1 h 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. By doing this, overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, animals were killed. The mesencephalon was processed for tyrosine hydroxylase (TH) immunocytochemistry. After 5 months of Mn mixture inhalation, mice developed evident deficits in their motor performance manifested as akinesia, postural instability and action tremor. SNc of the Mn-exposed animals showed an important decrease (67.58%) in the number of TH-immunopositive neurons. Our data provide evidence that MnCl(2) and Mn(OAc)(3) mixture inhalation produces similar morphological and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.

Matrix metalloproteinases 2 and 9 in central nervous system and their modification after vanadium inhalation.

Vanadium (V) derivatives are well-known environmental pollutants and its toxicity has been related with oxidative stress. Toxicity after vanadium inhalation on the substantia nigra, corpus striatum, hippocampus and ependymal epithelium was reported previously. The purpose of this study was to analyse the role of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) in the changes observed in brain tissue after chronic V inhalation. Mice were exposed to vaporized, vanadium pentoxide 0.02 m in deionized water for 1 h twice a week, and killed at 1 h, 1, 2 and 4 weeks after exposure. The brain was removed and the olfactory bulb, prefrontal cortex, striatum and hippocampus were dissected and the MMP content was obtained by zymography. The results showed that MMP-9 increased in all the structures at the end of the exposure, although in the hippocampus this increment was evident after 1 week of exposure. When MMP-2 was analysed in the olfactory bulb and prefrontal cortex it remained unchanged throughout the whole exposure, while in the hippocampus it increased at week 4, while in the striatum MMP-2 increased from the second week only, through the whole experiment. These results demonstrate that V increased MMPs in different structures of the CNS and this change might be associated with the previously reported modifications, such as dendritic spine loss and neuronal cell death. The modifications in MMPs could be related with blood-brain barrier (BBB) disruption which was reported previously. Oxidative stress might also be involved in the activation of these gelatinases as part of the different mechanisms which take place in V toxicity in the CNS.

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.

Nigrostriatal modifications after vanadium inhalation: an immunocytochemical and cytological approach.

Vanadium (V) has increased in the air as a component of suspended particles originated from fuel combustion. In this report, a model of inhaled V in mice was implemented to identify the effect that V has in the corpus striatum and substantia nigra, structures with high concentrations of dopamine and scarce antioxidants burden. Mice inhaled 0.02 M V2O5 1 h twice a week and were sacrificed at points from 1 to 8 weeks after inhalation, perfused, and processed for Golgi method and for tyroxine hidroxylase (TH) inmunocytochemistry. Cytological analysis consisted in counting the number of dendritic spines in 20 medium-size spiny neurons and the number of TH immunoreactive neurons in the substatia nigra pars compacta. Dendritic spine density decreased drastically after V exposure; the same was observed with the TH-positive neurons, which decreased in a time-dependent mode. No previous morphological studies about V and nervous system have been reported. The decrease in spine density and in TH-positive neurons might have functional repercussions that should be studied because the trend of this element in the atmosphere is to increase.

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.

Morphologic alteration of the olfactory bulb after acute ozone exposure in rats.

The interaction of ozone with some molecules results in an increased production of free radicals. The objective of this study was to identify whether acute ozone exposure to 1-1.5 ppm for 4 h, produced cytological and ultrastructural modifications in the olfactory bulb cells. The results showed that in rats exposed to ozone there was a significant loss of dendritic spines on primary and secondary dendrites of granule cells, whereas the control rats did not present such changes. Besides these exposed cells showed vacuolation of neuronal cytoplasm, swelling of Golgi apparatus and mitochondrion, dilation cisterns of the rough endoplasmic reticulum. These findings suggest that oxidative stress produced by ozone induces alterations in the granule layer of the olfactory bulb, which may be related to functional modifications.

Memory deterioration in an oxidative stress model and its correlation with cytological changes on rat hippocampus CA1.

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 memory and its correlation with the cytology of the hippocampus. Twenty-four male Wistar rats were exposed to 1 ppm (parts per million) ozone for 4 h in a closed chamber. Control group was exposed to flowing air. After ozone exposure, the rats were given long-term (24 h) memory training which consists of a passive avoidance conditioning. After that the animals were perfused and the brains were placed in the Golgi stain. The analysis consisted in counting the dendritic spines in five secondary and five tertiary dendrites of each of the 20 pyramidal neurons of hippocampus CA1 analyzed. Our results showed alterations on long-term memory and a significant reduction of dendritic spines, and provided evidence that this deterioration in memory is probably due to the reduction in spine density in the pyramidal neurons of hippocampus.