The plausibility of a role for mercury in the etiology of autism: a cellular perspective

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed

Neurotoxicity of Environmental Metal Toxicants

Environmental exposure to metallic neurotoxicants is a matter of growing concern since it may have very significant consequences for human health, from impairing neurodevelopment in children to the neurodegeneration processes involved in aging. The scientific community will face many challenges in identifying and preventing the adverse effects of environmental metal exposure on brain health. This collection of articles provides an overview of current work in the field of neurotoxicology of metal contaminants, from the identification of emerging toxic compounds, to the assessment of environmental exposures and associated risks, through the description of the molecular mechanisms involved in neurotoxicity

A Knowledge-based Integrative Modeling Approach for <em>In-Silico</em> Identification of Mechanistic Targets in Neurodegeneration with Focus on Alzheimer’s Disease

Dementia is the progressive decline in cognitive function due to damage or disease in the body beyond what might be expected from normal aging. Based on neuropathological and clinical criteria, dementia includes a spectrum of diseases, namely Alzheimer's dementia, Parkinson's dementia, Lewy Body disease, Alzheimer's dementia with Parkinson's, Pick's disease, Semantic dementia, and large and small vessel disease. It is thought that these disorders result from a combination of genetic and environmental risk factors. Despite accumulating knowledge that has been gained about pathophysiological and clinical characteristics of the disease, no coherent and integrative picture of molecular mechanisms underlying neurodegeneration in Alzheimer’s disease is available. Existing drugs only offer symptomatic relief to the patients and lack any efficient disease-modifying effects. The present research proposes a knowledge-based rationale towards integrative modeling of disease mechanism for identifying potential candidate targets and biomarkers in Alzheimer’s disease. Integrative disease modeling is an emerging knowledge-based paradigm in translational research that exploits the power of computational methods to collect, store, integrate, model and interpret accumulated disease information across different biological scales from molecules to phenotypes. It prepares the ground for transitioning from ‘descriptive’ to “mechanistic” representation of disease processes. The proposed approach was used to introduce an integrative framework, which integrates, on one hand, extracted knowledge from the literature using semantically supported text-mining technologies and, on the other hand, primary experimental data such as gene/protein expression or imaging readouts. The aim of such a hybrid integrative modeling approach was not only to provide a consolidated systems view on the disease mechanism as a whole but also to increase specificity and sensitivity of the mechanistic model by providing disease-specific context. This approach was successfully used for correlating clinical manifestations of the disease to their corresponding molecular events and led to the identification and modeling of three important mechanistic components underlying Alzheimer’s dementia, namely the CNS, the immune system and the endocrine components. These models were validated using a novel in-silico validation method, namely biomarker-guided pathway analysis and a pathway-based target identification approach was introduced, which resulted in the identification of the MAPK signaling pathway as a potential candidate target at the crossroad of the triad components underlying disease mechanism in Alzheimer’s dementia

2018 - The Twenty-third Annual Symposium of Student Scholars

The full program book from the Twenty-third Annual Symposium of Student Scholars, held on April 19, 2018. Includes abstracts from the presentations and posters.https://digitalcommons.kennesaw.edu/sssprograms/1020/thumbnail.jp

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Temas de actualidad en salud pública

La salud pública es una disciplina importante para la salud en el mundo. Se define como la ciencia y el arte de prevenir las enfermedades, prolongar la vida y promover la salud a través de los esfuerzos organizados y decisiones con conocimiento de la sociedad, las organizaciones (públicas y privadas), las comunidades y los individuos, esta disciplina se ha renovado con la incorporación de múltiples actores, profesiones, áreas de conocimiento, además de ser afectados y promovido por múltiples tecnologías, en particular los de información. Como un campo cambiante del conocimiento, la salud pública requiere la información basada en la evidencia y actualizaciones regulares, más aún en el contexto de un mundo en transición epidemiológica. "Temas actuales en la salud pública", presenta información actualizada sobre varios temas relacionados con las áreas reales de interés en esta ciencia médica creciente y emocionante, con la concepción y la filosofía que estamos trabajando para mejorar la salud de la población, en lugar que el tratamiento de las enfermedades de los pacientes individuales, la toma de decisiones sobre el cuidado de la salud colectiva que se basan en la mejor evidencia disponible, actualizada, válida y pertinente, y, finalmente, en el contexto de los recursos disponibles. La salud pública debe ser una ciencia compleja, ayudando en las decisiones, acciones y cambios en la salud del mundo. En una sociedad globalizada esto se hizo hincapié no sólo en una nación en particular, sino en todo el mundo.Public health is a major health discipline in the world. Defined as the science and art of preventing diseases, prolonging life and promoting health through the organized efforts and informed choices of the society, organizations (public and private), communities and individuals, this discipline has been renewed by the incorporation of multiple actors, professions, knowledge areas, as well as being impacted and promoted by multiple technologies, particularly information ones. As a changing field of knowledge, public health requires evidence-based information and regular updates, even more in the context of a world in epidemiological transition. Health impacts of climate change are currently in the quest of the Millennium Development Goals, and most of them are related to the activities of public health. “Current Topics in Public Health” presents updated information on multiple topics related to actual areas of interest in this growing and exciting medical science, with the conception and philosophy that we are working to improve the health of the population, rather than treating diseases of individual patients; taking decisions about collective health care that are based on the best available, current, valid and relevant evidence; and finally within the context of available resources. Public health should be a complex science helping in the decision, actions and changes in the health of the world. In a globalized society this is emphasized not just in a particular nation but in the whole world