Special Issue "Advances in Environmental Neurotoxicology"
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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601).
Deadline for manuscript submissions: closed (31 May 2011)
Special Issue Editor
Guest Editor
Prof. Dr. Stephen C. Bondy
Community & Environmental Medicine, Department of Medicine, University of California, Irvine, Irvine, CA 92697, USA
Website: http://www.faculty.uci.edu/profile.cfm?faculty_id=2283
E-Mail: scbondy@uci.edu
Phone: (949) 824-8077
Fax: (949) 824-2070
Interests: neurotoxicology; nutririon; aging; protein aggregates
Special Issue Information
Dear Colleagues,
In the past environmental toxicology focused on the hazards of relatively high exposure of toxicants, generally involving limited targets such as those working in specialized occupations or living in unusual places. More recent directions have emphasized the consequences of extended low-level exposures to much broader and general populations. It is increasing recognized that the rate of onset and progression of many age-related disease, especially those associated with nervous function, can be accelerated by environmental contaminants. Some prevalent neurological disorders associated with aging, are likely to be influenced by poorly understood environmental factors. This is especially so when they do not have a strong genetic basis and are idiopathic, such as Alzheimer's disease. In addition, some prevalent xenobiotic agents can impede developmental and maturational processes. This has been clearly shown in the case of very low levels of lead. Since such modifications of both ends of the life cycle represent merely an acceleration or retardation of ongoing normal events, they may be very difficult to identify. However, they can have serious societal consequences in view of the potential involvement of the entire population. This volume represent is intended to delineate some of the subtle changes associated with the chronic presence of toxicants in the general environment.
Prof. Dr. Stephen C. Bondy
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs).
Keywords
- toxicants
- neurological disease
- development
- aging
- population exposure
Published Papers (9 papers)
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Received: 31 December 2010; in revised form: 13 January 2011 / Accepted: 17 January 2011 / Published: 19 January 2011
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Abstract: The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial- encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1–6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides—picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity.
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Received: 10 February 2011; in revised form: 2 March 2011 / Accepted: 9 March 2011 / Published: 15 March 2011
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Abstract: Exposure to elements in groundwater (toxic or beneficial) is commonplace yet, outside of lead and mercury, little research has examined the impact of many commonly occurring environmental exposures on mental abilities during the aging process. Inorganic arsenic is a known neurotoxin that has both neurodevelopmental and neurocognitive consequences. The aim of this study was to examine the potential association between current and long-term arsenic exposure and detailed neuropsychological functioning in a sample of rural-dwelling adults and elders. Data were analyzed from 434 participants (133 men and 301 women) of Project FRONTIER, a community-based participatory research study of the epidemiology of health issues of rural-dwelling adults and elders. The results of the study showed that GIS-based groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning. Additionally, long-term low-level exposure to arsenic was significantly correlated to poorer scores in global cognition, processing speed and immediate memory. The finding of a correlation between arsenic and the domains of executive functioning and memory is of critical importance as these are cognitive domains that reflect the earliest manifestations of Alzheimer’s disease. Additional work is warranted given the population health implications associated with long-term low-level arsenic exposure.
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Received: 5 April 2011 / Accepted: 5 May 2011 / Published: 10 May 2011
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Abstract: Background: Workers chronically exposed to manganese in welding fumes may develop an extra-pyramidal syndrome with postural and action tremors. Objectives: To determine the utility of tremor analysis in distinguishing tremors among workers exposed to welding fumes, patients with Idiopathic Parkinson’s Disease (IPD) and Essential Tremor (ET). Methods: Retrospective study of recorded tremor in subjects from academic Movement Disorders Clinics and Welders. Quantitative tremor analysis was performed and associated with clinical status. Results: Postural tremor intensity was increased in Welders and ET and was associated with visibly greater amplitude of tremor with arms extended. Mean center frequencies (Cf) of welders and patients with ET were significantly higher than the mean Cf of PD subjects. Although both the welders and the ET group exhibited a higher Cf with arms extended, welders could be distinguished from the ET subjects by a significantly lower Cf of the rest tremor than that measured in ET subjects. Conclusions: In the context of an appropriate exposure history and neurological examination, tremor analysis may be useful in the diagnosis of manganese-related extra-pyramidal manifestations.
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Received: 14 April 2011; in revised form: 13 May 2011 / Accepted: 16 May 2011 / Published: 14 June 2011
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Abstract: This review explores the processes underlying the deleterious effects of the presence of insoluble or colloidal depositions within the central nervous system. These materials are chemically unreactive and can have a prolonged residence in the brain. They can be composed of mineral or proteinaceous materials of intrinsic or exogenous origin. Such nanoparticulates and colloids are associated with a range of slow-progressing neurodegenerative states. The potential common basis of toxicity of these materials is discussed. A shared feature of these disorders involves the appearance of deleterious inflammatory changes in the CNS. This may be due to extended and ineffective immune responses. Another aspect is the presence of excess levels of reactive oxygen species within the brain. In addition with their induction by inflammatory events, these may be further heightened by the presence of redox active transition metals to the large surface area afforded by nanoparticles and amphipathic micelles.
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Received: 5 May 2011; in revised form: 17 June 2011 / Accepted: 20 June 2011 / Published: 27 June 2011
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Abstract: Many times in the history of lead toxicology the view that “the problem” has been solved and is no longer a major health concern has prevailed, only to have further research demonstrate the prematurity of this judgment. In the last decade, an extraordinary amount of new research on lead has illustrated, all too clearly, that “the problem” has not disappeared, and that, in fact, it has dimensions never before considered. Recent risk assessments have concluded that research has yet to identify a threshold level below which lead can be considered “safe.” Although children’s intelligence has traditionally been considered to be the most sensitive endpoint, and used as the basis for risk assessment and standard setting, increased lead exposure has been associated with a wide variety of other morbidities both in children and adults, in some cases at biomarker levels comparable to those associated with IQ deficits in children. In adults, these endpoints include all-cause mortality and dysfunctions in the renal, cardiovascular, reproductive, central nervous systems. In children, IQ deficits are observed at blood lead levels well below 10 μg/dL, and the dose-effect relationship appears to be supra-linear. Other health endpoints associated with greater early-life lead exposure in children include ADHD, conduct disorder, aggression and delinquency, impaired dental health, and delayed sexual maturation. Studies employing neuroimaging modalities such as volumetric, diffusion tensor, and functional MRI are providing insights into the neural bases of the cognitive impairments associated with greater lead exposure.
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Received: 14 June 2011; in revised form: 5 July 2011 / Accepted: 13 July 2011 / Published: 20 July 2011
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Abstract: Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese and diesel exhaust particles.
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Received: 6 June 2011; in revised form: 9 September 2011 / Accepted: 9 September 2011 / Published: 16 September 2011
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Abstract: The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential.
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Received: 9 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 29 September 2011
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Abstract: Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, a disappearing neurodegenerative disease linked to use of the neurotoxic cycad plant for food and/or medicine, is intensively studied because the neuropathology (tauopathy) is similar to that of Alzheimer’s disease. Cycads contain neurotoxic and genotoxic principles, notably cycasin and methylazoxymethanol, the latter sharing chemical relations with nitrosamines, which are derived from nitrates and nitrites in preserved meats and fertilizers, and also used in the rubber and leather industries. This review includes new data that influence understanding of the neurobiological actions of cycad and related genotoxins and the putative mechanisms by which they might trigger neurodegenerative disease.
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Received: 15 November 2011; in revised form: 9 December 2011 / Accepted: 12 December 2011 / Published: 16 December 2011
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Abstract: Parkinson’s disease (PD) is a common neurodegenerative movement disorder that is characterized pathologically by a progressive loss of midbrain dopaminergic neurons and by protein inclusions, designated Lewy bodies and Lewy neurites. PD is one of the most common neurodegenerative diseases, affecting almost 1% of the population over 60 years old. Although the symptoms and neuropathology of PD have been well characterized, the underlying mechanisms and causes of the disease are still not clear. Genetic mutations can provide important clues to disease mechanism, but most PD cases are sporadic rather than familial; environmental factors have long been suspected to contribute to the disease. Although more than 90% of PD cases occur sporadically and are thought to be due, in part, to oxidative stress and mitochondrial dysfunction, the study of genetic mutations has provided great insight into the molecular mechanisms of PD. Furthermore, rotenone, a widely used pesticide, and paraquat and maneb cause a syndrome in rats and mice that mimics, both behaviorally and neurologically, the symptoms of PD. In the current review, we will discuss various aspects of gene-environment interaction that lead to progressive dopaminergic neurodegenration, mainly focusing on our current finding based on stress-mediated parkin dysfunction.
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Last update: 16 January 2012
