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David Pamies, Paula Barreras, Katharina Block, Georgia Makri, Anupama Kumar, Daphne Wiersma, Lenna Smirnova, Ce Zhang, Joseph Bressler, Kimberly M Christian, Georgina Harris, Guo-Li Ming, Cindy J Berlinicke, Kelly Kyro, Hongjun Song, Carlos A Pardo, Thomas Hartung, Helena T Hogberg
Human in-vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e...
November 24, 2016: ALTEX
Shaista Chaudhary, Upasana Sahu, Sudeshna Kar, Suhel Parvez
Phytanic acid, a saturated branched chain fatty acid and a major constituent of human diet, is predominantly found in dairy products, meat, and fish. It is a degradation product from the phytol side chain of chlorophyll. Degradation of PA is known to occur mainly in peroxisomes via α-oxidation and in mitochondria via β-oxidation. Due to its β-methyl group present at the 3-position of the carbon atoms, PA cannot be β-oxidized. Although alteration in the metabolism of PA may play an important role in neurodegeneration, the exact mechanism behind it remains to be evaluated...
October 26, 2016: Molecular Neurobiology
Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Robert F Halliwell
Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine...
October 11, 2016: Neurochemistry International
Susanna Alloisio, Patrizia Garbati, Federica Viti, Silvia Dante, Raffaella Barbieri, Giovanni Arnaldi, Alessia Petrelli, Arianna Gigoni, Paolo Giannoni, Rodolfo Quarto, Mario Nobile, Massimo Vassalli, Aldo Pagano
Recent advances in life sciences suggest that human and rodent cell responses to stimuli might differ significantly. In this context, the results achieved in neurotoxicology and biomedical research practices using neural networks obtained from mouse or rat primary culture of neurons would benefit of the parallel evaluation of the same parameters using fully differentiated neurons with a human genetic background, thus emphasizing the current need of neuronal cells with human origin. In this work, we developed a human functionally active neural network derived by human neuroblastoma cancer cells genetically engineered to overexpress NDM29, a non-coding RNA whose increased synthesis causes the differentiation toward a neuronal phenotype...
October 3, 2016: Molecular Neurobiology
Joan M Cranmer
No abstract text is available yet for this article.
September 2016: Neurotoxicology
A C Sintov, C Velasco-Aguirre, E Gallardo-Toledo, E Araya, M J Kogan
Metal nanoparticles have been proposed as a carrier and a therapeutic agent in biomedical field because of their unique physiochemical properties. Due to these physicochemical properties, they can be used in different fields of biomedicine. In relation to this, plasmonic nanoparticles can be used for detection and photothermal destruction of tumor cells or toxic protein aggregates, and magnetic iron nanoparticles can be used for imaging and for hyperthermia of tumor cells. In addition, both therapy and imaging can be combined in one nanoparticle system, in a process called theranostics...
2016: International Review of Neurobiology
Ming Li, Shuo Zhou, Xian-Song Wang, Ci Liu, Shu Li
Avermectins (AVMs) are used worldwide in agriculture and veterinary medicine. Residues of avermectin drugs, causing toxicological effects on non-target organisms, have raised great concern. The aim of this study was to investigate the effects of AVM on the expression levels of alpha synuclein (α-Syn) and proteasomal activity in pigeon (Columba livia) neurons both in vivo and in vitro. The results showed that, the mRNA and protein levels of α-Syn increased in AVM treated groups relative to control groups in the cerebrum, cerebellum and optic lobe in vivo...
September 24, 2016: Ecotoxicology and Environmental Safety
Ifukibot Levi Usende, Dominque F Leitner, Elizabeth Neely, James R Connor, James O Olopade
Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental exposure to vanadium, a transition metal can disrupt this iron homeostasis. We investigated the interaction of iron deficiency and vanadium exposure on the myelination infrastructure and its related neurobehavioural phenotypes, and neurocellular profiles in developing rat brains...
2016: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
Sufang Wang, Qiyan Lv, Yu Yang, Liang-Hong Guo, Bin Wan, Xiaomin Ren, Hui Zhang
Mercury compounds are well-known toxic environmental pollutants and potently induce severe neurotoxicological effects in human and experimental animals. Previous studies showed that one of the mechanisms of mercury compounds neurotoxicity arose from the over-activation of the N-methyl d-aspartate (NMDA)-type glutamate receptor induced by increased glutamate release. In this work, we aimed to investigate the molecular mechanisms of Hg compounds neurotoxicities by identifying their biological targets in cells...
October 15, 2016: Biochemical Pharmacology
Ruth Bevan, Lini Ashdown, Doreen McGough, Alicia-Huici Montagaud, Leonard Levy
In 2004, a review by the Institute of Environment and Health (IEH) made recommendations on occupational exposure limits (OELs) for manganese and its inorganic compounds for inhalable and respirable fractions respectively. These OELs were based on a detailed comprehensive evaluation of all the scientific data available at that time. Since then, more published studies have become available and a number of occupational standard-setting committees (EU SCOEL, US ACGIH-TLV, and Germany MAK) have proposed OEL's for manganese and its inorganic compounds that are somewhat lower that those proposed in the 2004 review...
August 9, 2016: Neurotoxicology
Danielle Hagstrom, Olivier Cochet-Escartin, Eva-Maria S Collins
Freshwater planarians, famous for their regenerative prowess, have long been recognized as a valuable in vivo animal model to study the effects of chemical exposure. In this review, we summarize the current techniques and tools used in the literature to assess toxicity in the planarian system. We focus on the planarian's particular amenability for neurotoxicology and neuroregeneration studies, owing to the planarian's unique ability to regenerate a centralized nervous system. Zooming in from the organismal to the molecular level, we show that planarians offer a repertoire of morphological and behavioral readouts while also being amenable to mechanistic studies of compound toxicity...
April 2016: Regeneration
Béla Z Schmidt, Martin Lehmann, Simon Gutbier, Erastus Nembo, Sabrina Noel, Lena Smirnova, Anna Forsby, Jürgen Hescheler, Hasan X Avci, Thomas Hartung, Marcel Leist, Julianna Kobolák, András Dinnyés
Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells...
August 4, 2016: Archives of Toxicology
Deborah Bennett, David C Bellinger, Linda S Birnbaum, Asa Bradman, Aimin Chen, Deborah A Cory-Slechta, Stephanie M Engel, M Daniele Fallin, Alycia Halladay, Russ Hauser, Irva Hertz-Picciotto, Carol F Kwiatkowski, Bruce P Lanphear, Emily Marquez, Melanie Marty, Jennifer McPartland, Craig J Newschaffer, Devon Payne-Sturges, Heather B Patisaul, Frederica P Perera, Beate Ritz, Jennifer Sass, Susan L Schantz, Thomas F Webster, Robin M Whyatt, Tracey J Woodruff, R Thomas Zoeller, Laura Anderko, Carla Campbell, Jeanne A Conry, Nathaniel DeNicola, Robert M Gould, Deborah Hirtz, Katie Huffling, Philip J Landrigan, Arthur Lavin, Mark Miller, Mark A Mitchell, Leslie Rubin, Ted Schettler, Ho Luong Tran, Annie Acosta, Charlotte Brody, Elise Miller, Pamela Miller, Maureen Swanson, Nsedu Obot Witherspoon
No abstract text is available yet for this article.
July 1, 2016: Environmental Health Perspectives
Michelle C Janelsins, Charles E Heckler, Bryan D Thompson, Robert A Gross, Lisa A Opanashuk, Deborah A Cory-Slechta
BACKGROUND: Cyclophosphamide chemotherapy is a mainstay of adjuvant breast cancer treatment. Unfortunately, this drug is associated with cognitive impairments in cancer patients that may accelerate cognitive aging. Memory is particularly affected in many patients. In order to better understand the precise cognitive impairments caused by this chemotherapy agent, we investigated a clinically relevant dose and administration paradigm on delayed spatial memory abilities in C57BL/6 mice. We utilized a delayed alternation paradigm similar to a delayed match to sample paradigm reported to be sensitive in neurotoxicology research...
June 28, 2016: Neurotoxicology
Antonio Planchart, Carolyn J Mattingly, David Allen, Patricia Ceger, Warren Casey, David Hinton, Jyotshna Kanungo, Seth W Kullman, Tamara Tal, Maria Bondesson, Shawn M Burgess, Con Sullivan, Carol Kim, Mamta Behl, Stephanie Padilla, David M Reif, Robert L Tanguay, Jon Hamm
Small freshwater fish models, especially zebrafish,offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity...
June 21, 2016: ALTEX
Juliana Faria, Joana Barbosa, Odília Queirós, Roxana Moreira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling...
June 1, 2016: Toxicology
Jamie DeWitt, Brenda Buck, Dirk Goossens, Qing Hu, Rebecca Chow, Winnie David, Sharon Young, Yuanxin Teng, Mallory Leetham-Spencer, Lacey Murphy, James Pollard, Brett McLaurin, Russell Gerads, Deborah Keil
Geogenic dust from arid environments is a possible inhalation hazard for humans, especially when using off-road vehicles that generate significant dust. This study focused on immunotoxicological and neurotoxicological effects following subacute exposure to geogenic dust generated from sediments in the Nellis Dunes Recreation Area near Las Vegas, Nevada that are particularly high in arsenic; the naturally-occurring arsenic concentrations in these surficial sediments ranged from 4.8 to 346μg/g. Dust samples from sediments used in this study had a median diameter of 4...
August 1, 2016: Toxicology and Applied Pharmacology
Rongwei Zhai, Na Zheng, Joshua Rizak, Xintian Hu
Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain...
2016: Analytical Cellular Pathology (Amsterdam)
Andrew D Kraft, Michael Aschner, Deborah A Cory-Slechta, Staci D Bilbo, W Michael Caudle, Susan L Makris
Silent neurotoxicity, a term introduced approximately 25years ago, is defined as a persistent change to the nervous system that does not manifest as overt evidence of toxicity (i.e. it remains clinically unapparent) unless unmasked by experimental or natural processes. Silent neurotoxicants can be challenging for risk assessors, as the multifactorial experiments needed to reveal their effects are seldom conducted, and they are not addressed by current study design guidelines. This topic was the focus of a symposium addressing the interpretation and use of silent neurotoxicity data in human health risk assessments of environmental toxicants at the annual meeting of the Developmental Neurotoxicology Society (previously the Neurobehavioral Teratology Society) on June 30th, 2014...
May 2016: Neurotoxicology and Teratology
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