Hippocampal-related memory deficits and histological damage induced by neonatal ionizing radiation exposure. Role of oxidative status.

Ionizing radiations induce oxidative stress on target tissues, mainly through the generation of reactive oxygen species (ROS). However, there are few data available on the behavioral effects of moderate doses of ionizing radiation. The aim of the present work was to evaluate the performance of adult rats irradiated at birth in different hippocampal-dependent behavioral tasks and to establish a relationship with the oxidative status and histological changes in rat hippocampus (Hip). Male Wistar rats were irradiated with 5 Gy of X rays between 24 and 48 h after birth. Thirty days later, rats were subjected to open field, object recognition and inhibitory avoidance tasks. In addition, oxidative status markers as well as protein kinase C (PKC) activity and histological changes were assessed in control and irradiated Hip. Results show an impairment in recognition and habituation memories in 30-day-old animals exposed to neonatal ionizing radiation, both at short- (ST) and at long-term (LT), whereas an improvement in associative memory was observed at ST. In addition, histological alterations were observed in irradiated Hip. Although an increase in ROS levels and PKC activity were found in irradiated Hip, no changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were observed. Taken together, our results support the hypothesis that an increased PKC activity, induced by neonatal ionizing radiation on rat Hip, could play a role in the generation of an imbalance between ROS levels and antioxidant systems and might underlie radiation-induced hippocampal histological damage as well as the Hip-dependent behavioral changes found in irradiated rats.

Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

The role of catechols and free radicals in benzene toxicity: an oxidative DNA damage pathway.

Benzene is a widespread volatile compound and an environmental contaminant. Since it causes important toxic effects in workers exposed to low levels, long-term exposure to this compound has been extensively studied. Leukemia, blood disorders, bone marrow depression, and some types of cancer are directly related to benzene-initiated toxicity. Bioactivation of benzene can lead to the formation of hazardous metabolites such as phenol, hydroquinone, and catechol. Catechol forms semiquinones and reactive quinones that are presumed to play an important role in the generation of reactive oxygen species (ROS). ROS formation can directly induce single and double strand breaks in the DNA, oxidized nucleotides, and hyper-recombination, and consequently produces deleterious genetic changes. In this review, we have addressed the cytotoxic effects of benzene and its main metabolite, catechol, focusing on the oxidative pathway and further DNA damage.

Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease.

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. The potential cytoprotective effects of aqueous extract of Valeriana officinalis on rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells were demonstrated. The cytotoxicity, cell viability and analysis of cellular morphology were performed by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and phase contrast microscopy, respectively. Significant changes in the cellular morphology, and condensation of the cell body could be observed when cells were treated with 300 nM rotenone for 48 h. Three different concentrations of Valeriana officinalis extract were used (0.049, 0.098 and 0.195 mg/mL). These extracts brought about an increase of 7.0 +/- 1.3%, 14.5 +/- 1.3% and 14.5 +/- 3.2% in cell viability. Our results indicated that neuroprotector action of the Valeriana officinalis extract provides support for later studies as they help understanding this drug for the development of cytoprotective various therapies in PD.

A tridimensional view of the organization of actin filaments in the central nervous system by use of fluorescent photooxidation.

Cellular and subcellular organization and distribution of actin filaments have been studied with various techniques. The use of fluorescence photo-oxidation combined with phalloidin conjugates with eosin has allowed the examination of the precise cellular and subcellular location of F-actin. Correlative fluorescence light microscopy and transmission electron microscopy studies of F-actin distribution are facilitated with this method for morphological and physiological studies. Because phalloidin-eosin is smaller than other markers, this method allows the analysis of the three-dimensional location of F-actin with high-resolution light microscopy, three-d serial sections reconstructions, and electron tomography. The combination of selective staining and three-dimensional reconstructions provide a valuable tool for revealing aspects of the synaptic morphology that are not available when conventional electron microscopy is used. By applying this selective staining technique and three-dimensional imaging, we uncovered the structural organization of actin in the postsynaptic densities in physiological and pathological conditions.