Exposure to methyl mercury (MeHg) is a global concern. Increased chronic exposure to MeHg among fish and marine mammal consuming populations will increase the risk of prenatal exposure and as a result, the risk of infant brain damage and neurotoxcity. It is therefore important to understand the role of environmental factors, such as nutrition, in determining susceptibility to MeHg toxicity. Three nutrients (selenium (Se), vitamin C and vitamin E) were selected for examination of their interactions with the mechanisms of McHg cytotoxicity in vitro. Two hybrid neural cell lines (M03.13 and NSC-34) were evaluated for their usefulness in the study of MeHg cytotoxicity. Sixteen toxic endpoints were selected for investigation of growth, viability, structure and biochemistry. Both cell lines responded to MeHg exposure in a dose dependent manner for the majority of endpoints suggesting that both MO3.13 and NSC-34 cells undergo structural and biochemical changes during exposure to McHg, but that MO3.13 cells are more sensitive to DNA, mitochondria) membrane damage and glutathione (GSH) depletion and that NSC-34 cells are more sensitive to protein damage and apoptosis. Se exposure lessened the MeHg-induced decrease in DNA and GSH concentrations in both cell lines. In NSC-34 cells, Se also increased F-actin concentrations and prevented an increase in caspase-3 activity. Se may alter the mechanism of cell death by preventing McHg disruption of DNA replication thus maintaining the production and function of peptides (GSH) and protein (polymerized actin) that aid in MeHg detoxification and neural function. In NSC-34 cells, vitamin C prevented the induction of caspase-3 activity and lessened DNA damage and GSH depletion. Vitamin E lessened GSH depletion and lessened G-actin depletion. Both vitamin C and E improved GSH status, but vitamin C also delayed McHg damage of DNA and prevented early signs of apoptosis suggesting these two vitamins interfere with MeHg metabolism by diffe

Methylmercury (MeHg) is an environmental contaminant mainly present in fish and seafood. The long-term consumption of these fish and seafoods could pose a health risk to pregnant women and their children. Animal studies were conducted to assess the effects of MeHg exposure on reproduction and offspring development as well as the potential benefits of nutrient supplementation. Adult female rats were treated by gavage with MeHg at dose levels of 0.5, 1.0 or 2.0 mg/kg/day for 4 weeks prior to mating and throughout pregnancy, and then were allowed to deliver. In a second study, adult female rats were treated with MeHg at 1.25 mg/kg/day for the same duration, and they were fed diets containing an extra 1 ppm selenium (Se), or 225 IU/kg vitamin E, or both of these two nutrients, 4 weeks prior to MeHg dosing, and then throughout McHg treatment. (Abstract shortened by UMI.)

White blood cell phagocytosis was investigated and used with avian blood, and assessed as a potential biomarker for mercury immunotoxicity in free ranging birds (common loons). Phagocytosis is an essential immunological function and can be measured using flow cytometry. The assay was assessed with in vitro exposure using whole blood and isolated white blood cells (WBC) from domestic chickens, and with in vivo exposure using whole blood from captive doves and wild loons. McHg at 0.1ppm significantly depressed phagocytic capacity of isolated WBCs without affecting their viability, but did not affect phagocytic activity when added to whole blood up to 50ppm. Also, no significant relationship between blood-Hg level and phagocytic capacity of WBCs was observed in ringed turtle doves fed McHg in their diets, nor in wild common loons having a range of blood-Hg concentrations. The phagocytosis assay is a convenient assay for use in field studies of free-living birds, but is not responsive to McHg exposure in birds, and so is not recommended as a biomarker of immunotoxicity in Hg-exposed loons.

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The thesis examines aspects of the construction of methylmercury as an authoritative object of knowledge for Chisasibi, a Cree community on the James Bay coast in northern Quebec. I describe the evolution of a particular set of spheres of exchange which mediate economic relations between the Cree communities, the governments of Quebec and Canada, and state and corporate structures tied to the state. Knowledge claims about mercury can be seen as situated among claims of injury in a moral economy which is based on conflict over the James Bay hydro-electric project. The politicization and subsequent medicalization of these knowledge claims are described. Finally, I trace the emergence of particular concepts of 'normality', 'risk' and 'risk group' in medical and technocratic discourses about the effects of methylmercury on Canadian aboriginal populations.

Sprague-Dawley rats were administered daily, subcutaneous injections of methylmercuric chloride at a dose of 5 mg/Hg/kg beginning on postnatal day 5. By their fourth postnatal week, animals exhibited a constellation of neurological signs of motor impairment which resembled the cerebral palsy syndrome of humans perinatally exposed to methylmercury. Routine histological examination of the brain revealed no gross differences between methylmercury-treated (MeHg), normal control (NC) or weight-matched littermates. The histochemical localization of the mitochondrial enzyme cytochrome oxidase (CO) was utilized in Experiment I to examine possible alterations in the metabolic activity of motor nuclei which might contribute to the observed movement and postural disorders. A population of intensely-staining cytochrome oxidase neurons (ICONs) in the magnocellular portion of the red nucleus (RMC) and interrubral mesencephalon (IRM) were conspicuously present in all MeHg animals at the onset of motor impairment. These morphologically, histochemically, and anatomically distinct neurons did not exhibit intense CO staining in control animals. Conversely, a significant decrease was demonstrated in the oxidative metabolic activity of many neurons in the substantia nigra, zona reticulata of MeHg animals. In Experiment II, the postnatal appearance of ICONs was morphometrically quantified in MeHg animals sacrificed at PND 14, 16, 18, 20, 22, or 25. The histochemically-defined onset of increased metabolic activity in ICONs was first observed on PND 16, at least one week before the onset of clinical signs of neurological impairment. This was the earliest manifestation of methylmercury neurotoxicity yet described in this animal model. A subsequent four-fold increase in the total number of ICONs at PND 18 was followed by a gradual decrease in number to PND 25. Significantly more of the ICONs were found in the IRM than in the RMC at PND 18 & 20. The possibility that the increased activity of ICONs may result from disinhibition of specific afferents to the red nucleus was addressed by introducing either hemidecortication or hemicerebellectomy on PND 10 and then morphometrically determining the deviation from symmetry in the bilateral distribution of the total number of ICONs in the RMC and IRM at PND 22. The distribution of ICONs was symmetrical and not different in either hemidecorticate or unoperated controls. A significant (36%) decrease in the total number of ICONs was observed in both the RMC and IRM contralateral to hemicerebellectomy. The identical ipsilateral regions did not differ from control or hemidecorticate MeHg animals. In Experiment III, the anatomical distribution of major histocompatability complex antigens (MHC) in the brain of MeHg animals was examined using immunohistochemical methods. MHC immunoreactivity was widely distributed throughout the brain of MeHg animals. Areas with low immunoreactivity, or lack of it, stand out and include all of the hippocampus, thalamus, pyriform and entorhinal cortex, and lateral cerebellar hemispheres. Moderate staining intensity was observed in neocortical areas, basal forebrain, caudate-putamen and cerebellar vermis. Strong immunoreactivity was found in red nucleus, substantia nigra, cingulate cortex, retrosplenial cortex, presubiculum, parasubiculum and vestibular nuclei. It was suggested that the increased activity of ICONs likely contributes to the movement and postural disorders resulting from methylmercury intoxication. The increased activity in ICONs was determined to be, at least partially, dependent upon cerebellar input. The results are discussed with reference to the toxic effects of methylmercury and specifically to the susceptibility of GABAergic interneurons in perinatal trauma. Possible analogies are drawn between the mechanisms of methylmercury-induced cerebral palsy syndrome and those of other developmental movement and postural disorders. / Medicine, Faculty of / Graduate

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Kwok, Ka Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 124-146). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / LIST OF FIGURE --- p.ix / ABBREVIATIONS / For Units --- p.x / For Prefixes of the International System of Units --- p.x / For Terms Commonly Used --- p.xi / Role of research workers --- p.xv / Chapter CHAPTER 1 --- Overview of methylmercury / Chapter 1.1 --- Source of methylmercury --- p.1 / Chapter 1.2 --- Toxicokinetics --- p.3 / Chapter 1.2.1 --- Absorption and distribution --- p.3 / Chapter 1.2.2 --- Half-life --- p.5 / Chapter 1.2.3 --- Metabolism/Biotransformation --- p.5 / Chapter 1.2.4 --- Biochemical mechanism of toxicity --- p.7 / Chapter 1.3 --- Health effects of mercury exposure --- p.9 / Chapter 1.3.1 --- Adult central nervous system --- p.10 / Chapter 1.3.2 --- The developing central nervous system --- p.11 / Chapter 1.3.3 --- Cardiovascular effects --- p.13 / Chapter 1.3.4 --- Immunotoxicity --- p.14 / Chapter 1.4 --- Biomarkers for prenatal exposure --- p.15 / Chapter 1.5 --- MeHg exposure in high risk populations in Hong Kong --- p.17 / Chapter CHAPTER 2 --- Neurocognitive performance / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- New Zealand --- p.20 / Chapter 2.1.2 --- Seychelles --- p.21 / Chapter 2.1.3 --- Faroe Islands --- p.22 / Chapter 2.1.4 --- The Hong Kong situation --- p.23 / Chapter 2.2 --- Method --- p.23 / Chapter 2.2.1 --- Subjects and study design --- p.23 / Chapter 2.2.2 --- Questionnaires --- p.24 / Chapter 2.2.3 --- Hg concentration measurement --- p.25 / Chapter 2.2.4 --- Neurocognitive measurements --- p.26 / Chapter 2.2.4.1 --- Hong Kong - Wechsler Intelligence Scale for Children --- p.27 / Chapter 2.2.4.2 --- Hong King List Learning Test --- p.28 / Chapter 2.2.4.3 --- Test of Everyday Attention for Children --- p.29 / Chapter 2.2.4.4 --- Boston Naming Test --- p.31 / Chapter 2.2.4.5 --- Grooved Pegboard Test --- p.31 / Chapter 2.2.5 --- Statistical analysis --- p.32 / Chapter 2.3 --- Results --- p.33 / Chapter 2.3.1 --- Subject characteristic --- p.33 / Chapter 2.3.2 --- Test results --- p.34 / Chapter 2.3.3 --- Statistical analysis results --- p.35 / Chapter 2.4 --- Discussion --- p.36 / Chapter CHAPTER 3 --- Cardiac autonomic function / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.1.1 --- Mechanism --- p.60 / Chapter 3.1.2 --- The association between HRV and the ANS --- p.61 / Chapter 3.1.3 --- Clinical applications and related studies --- p.63 / Chapter 3.1.4 --- Associations between MeHg exposure & HRV --- p.64 / Chapter 3.2 --- Methods --- p.65 / Chapter 3.2.1 --- Subjects and study design --- p.65 / Chapter 3.2.2 --- Physical and HRV measurement --- p.66 / Chapter 3.2.3 --- Time domain analysis --- p.68 / Chapter 3.2.4 --- Frequency domain analysis --- p.68 / Chapter 3.2.5 --- Non-linear method --- p.69 / Chapter 3.2.6 --- Statistical analysis --- p.70 / Chapter 3.3 --- Results --- p.71 / Chapter 3.3.1 --- Subjects characteristics --- p.71 / Chapter 3.3.2 --- HRV and statistical analysis results --- p.71 / Chapter 3.4 --- Discussion --- p.73 / Chapter CHAPTER 4 --- Immuno-toxicity / Chapter 4.1 --- Introduction --- p.91 / Chapter 4.2 --- Methods --- p.96 / Chapter 4.2.1 --- Subjects and Study Design --- p.96 / Chapter 4.2.2 --- Cytokine measurement --- p.96 / Chapter 4.2.3 --- Reversibility --- p.98 / Chapter 4.2.4 --- Statistical Analysis --- p.99 / Chapter 4.3 --- Results --- p.101 / Chapter 4.3.1 --- Subject Characteristics --- p.101 / Chapter 4.3.2 --- Atopic and non-atopic diseases group --- p.101 / Chapter 4.3.3 --- Cytokine profiles --- p.102 / Chapter 4.3.4 --- Reversibility --- p.103 / Chapter 4.4 --- Discussion --- p.104 / Chapter CHAPTER 5 --- Conclusion --- p.119 / Reference List --- p.124