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Wang D.,West Virginia University | Wang D.,Blanchette Rockefeller Neurosciences Institute | Zheng W.,Blanchette Rockefeller Neurosciences Institute | Zheng W.,Pathology and Physiology Research Branch
Brain Research | Year: 2015

Previous studies have shown dietary cholesterol can enhance learning but retard memory which may be partly due to increased cholesterol levels in hippocampus and reduced afterhyperpolarization (AHP) amplitude of hippocampal CA1 neurons. This study explored the dose-dependent effect of dietary cholesterol on synaptic plasticity of rabbit hippocampal CA1 neurons and spine morphology, the postsynaptic structures responsible for synaptic plasticity. Field potential recordings revealed a low concentration of dietary cholesterol increased long-term potentiation (LTP) expression while high concentrations produced a pronounced reduction in LTP expression. Dietary cholesterol facilitated basal synaptic transmission but did not influence presynaptic function. DiI staining showed dietary cholesterol induced alterations in dendrite spine morphology characterized by increased mushroom spine density and decreased thin spine density, two kinds of dendritic spines that may be linked to memory consolidation and learning acquisition. Dietary cholesterol also modulated the geometric measures of mushroom spines. Therefore, dietary cholesterol dose-dependently modulated both synaptic plasticity and dendrite spine morphologies of hippocampal CA1 neurons that could mediate learning and memory changes previously seen to result from feeding a cholesterol diet. © 2015 Elsevier B.V. All rights reserved.

Golokhvast K.S.,Far Eastern Federal University | Shvedova A.A.,Pathology and Physiology Research Branch | Shvedova A.A.,West Virginia University
PLoS ONE | Year: 2014

Galvanic manufacturing is widely employed and can be found in nearly every average city in Russia. The release and accumulation of different metals (Me), depending on the technology used can be found in the vicinities of galvanic plants. Under the environmental protection act in Russia, the regulations for galvanic manufacturing do not include the regulations and safety standards for ambient ultrafine and nanosized particulate matter (PM). To assess whether Me nanoparticles (NP) are among environmental pollutants caused by galvanic manufacturing, the level of Me NP were tested in urban snow samples collected around galvanic enterprises in two cities. Employing transmission electronic microscopy, energy-dispersive X-ray spectroscopy, and a laser diffraction particle size analyzer, we found that the size distribution of tested Me NP was within 10-120 nm range. This is the first study to report that Me NP of Fe, Cr, Pb, Al, Ni, Cu, and Zn were detected around galvanic shop settings. © 2014 Golokhvast, Shvedova.

Andon F.T.,Karolinska Institutet | Kapralov A.A.,University of Pittsburgh | Yanamala N.,Pathology and Physiology Research Branch | Feng W.,University of Pittsburgh | And 14 more authors.
Small | Year: 2013

Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kisin E.R.,Pathology and Physiology Research Branch | Yanamala N.,Pathology and Physiology Research Branch | Farcas M.T.,Pathology and Physiology Research Branch | Gutkin D.W.,University of Pittsburgh | And 5 more authors.
Environmental and Molecular Mutagenesis | Year: 2015

Altering the fuel source from petroleum-based ultralow sulfur diesel to biodiesel and its blends is considered by many to be a sustainable choice for controlling exposures to particulate material. As the exhaust of biodiesel/diesel blends is composed of a combination of combustion products of polycyclic aromatic hydrocarbons and fatty acid methyl esters, we hypothesize that 50% biodiesel/diesel blend (BD50) exposure could induce harmful outcomes because of its ability to trigger oxidative damage. Here, adverse effects were compared in murine male reproductive organs after pharyngeal aspiration with particles generated by engine fueled with BD50 or neat petroleum diesel (D100). When compared with D100, exposure to BD50 significantly altered sperm integrity, including concentration, motility, and morphological abnormalities, as well as increasing testosterone levels in testes during the time course postexposure. Serum level of luteinizing hormone was significantly depleted only after BD50 exposure. Moreover, we observed that exposure to BD50 significantly increased sperm DNA fragmentation and the upregulation of inflammatory cytokines in the serum and testes on Day 7 postexposure when compared with D100. Histological evaluation of testes sections from BD50 exposure indicated more noticeable interstitial edema, degenerating spermatocytes, and dystrophic seminiferous tubules with arrested spermatogenesis. Significant differences in the level of oxidative stress assessed by accumulation of lipid peroxidation products and depletion of glutathione were detected on exposure to respirable BD50 and D100. Taken together, these results indicate that exposure of mice to inhalable BD50 caused more pronounced adverse effects on male reproductive function than diesel. © 2014 Wiley Periodicals, Inc.

Mercer R.R.,Pathology and Physiology Research Branch | Mercer R.R.,West Virginia University | Hubbs A.F.,Pathology and Physiology Research Branch | Scabilloni J.F.,Pathology and Physiology Research Branch | And 6 more authors.
Particle and Fibre Toxicology | Year: 2011

Multi-walled carbon nanotubes (MWCNTs) are new manufactured nanomaterials with a wide spectrum of commercial applications. To address the hypothesis that MWCNTs cause persistent pulmonary pathology, C57BL/6J mice were exposed by pharyngeal aspiration to 10, 20, 40 or 80 μg of MWCNTs (mean dimensions of 3.9 μm × 49 nm) or vehicle. Lungs were preserved at 1, 7, 28 and 56 days post- exposure to determine the potential regions and target cells for impact by MWCNT lung burden. Morphometric measurement of Sirius Red staining was used to assess the connective tissue response.Results: At 56 days post-exposure, 68.7 ± 3.9, 7.5 ± 1.9 and 22.0 ± 5.1 percent (mean ± SE, N = 8) of the MWCNT lung burden were in alveolar macrophages, alveolar tissue and granulomatous lesions, respectively. The subpleural tissues contained 1.6% of the MWCNT lung burden. No MWCNTs were found in the airways at 7, 28 or 56 days after aspiration The connective tissue in the alveolar interstitium demonstrated a progressive increase in thickness over time in the 80 μg exposure group (0.12 ± 0.01, 0.12 ± 0.01, 0.16 ± 0.01 and 0.19 ± 0.01 μm for 1, 7, 28 and 56 days post-exposure (mean ± SE, N = 8)). Dose-response determined at 56 days post-exposure for the average thickness of connective tissue in alveolar septa was 0.11 ± 0.01, 0.14 ± .02, 0.14 ± 0.01, 0.16 ± 0.01 and 0.19 ± 0.01 μm (mean ± SE, N = 8) for vehicle, 10, 20, 40 and 80 μg dose groups, respectively.Conclusions: The distribution of lung burden was predominately within alveolar macrophages with approximately 8% delivery to the alveolar septa, and a smaller but potentially significant burden to the subpleural tissues. Despite the relatively low fraction of the lung burden being delivered to the alveolar tissue, the average thickness of connective tissue in the alveolar septa was increased over vehicle control by 45% in the 40 μg and 73% in the 80 μg exposure groups. The results demonstrate that MWCNTs have the potential to produce a progressive, fibrotic response in the alveolar tissues of the lungs. However, the increases in connective tissue per μg dose of MWCNTs to the interstitium are significantly less than those previously found for single-walled carbon nanotubes (SWCNTs). © 2011 Mercer et al; licensee BioMed Central Ltd.

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