Methylmercury (MeHg) is a neurotoxic global pollutant that accumulates at high levels in predatory fish and marine mammals. The dietary intake of these animals is the main source of MeHg exposure in humans. At high levels, MeHg is known to damage the sensory and motor systems in both adults and children. Due to the complexity and inaccessibility of the central nervous system (CNS), early dysfunction is difficult to detect. Biochemical markers in the CNS have been used to identify MeHg neurotoxicity in animal models. Analogues of these biochemical targets are also present in peripheral blood tissue and may reflect early CNS dysfunction in human populations. The proposed peripheral biomarkers include (1) lymphocyte muscarinic acetylcholine (mACh) receptor, (2) serum cholinesterase (ChE) and (3) platelet monoamine oxidase (MAO). This thesis evaluates the effects of mercury (Hg) compounds on these CNS and peripheral biochemical markers in laboratory and epidemiological studies. In vitro studies showed that inorganic Hg (HgCl2) and MeHg inhibited mACh receptor binding in human, rat, and mouse brain tissue. Additionally, studies demonstrated that a low-level gestational exposure to MeHg reduced MAO activity in the developing embryo and in adult female offspring. Combined, these studies provide a framework for the assessment of biochemical targets of Hg compounds in humans. A cross sectional study was conducted to evaluate the association between peripheral biochemical markers and MeHg exposure in fish-eating adults (n=129) from Lac St-Pierre, Quebec. Blood-Hg concentrations were used as a marker of exposure and ranged from 0.2 to 17.0 mug/L. Multiple linear regression analysis demonstrated that both blood-Hg (p=0.011) and heavy smoking (p=0.001) were associated with reduced platelet-MAO activity. However, neither lymphocyte mACh receptor nor serum ChE was related to blood-Hg. These results suggest that exposure to MeHg may result in reduced plat

520 L $$aIn the CNS, myelination of axons is essential for the rapid conduction of impulses down the nerve. In demyelinated or failing axons however, conduction is less efficient and requires more energy. The principal function of mitochondria is to provide energy for the axon but in doing so they generate most of the intra-axonal reactive oxygen species (ROS). Therefore and increased energy requirement will promote an increased production of ROS which could lead to significant damage to essential DNA, proteins and lipids and could eventually damage the axon. This thesis investigates the mitochondrial involvement in axonal pathology in the CNS diseases, multiple sclerosis (MS), autosomal dominant optic atrophy (ADOA) and tosomal dominant optic atrophy with cataract (ADOAC).

No description available.

As one of the closest relatives of arthropods, Onychophora plays an important role in understanding the evolution of arthropod body plans. Currently there is controversy surrounding the evolution of the brain among the ecdysozoan clades, which shows a collar-shaped, circumoral organization in cycloneuralians but a ganglionic architecture in panarthropods. Based on the innervation pattern of lip papillae surrounding the mouth, the onychophoran brain has been interpreted as a circumoral ring, suggesting that this organization is an ancestral feature of Ecdysozoa. However, this interpretation is inconsistent with other published data. To explore the evolutionary origin of the onychophoran mouth and to shed light on the evolution of the ecdysozoan brains, we analyzed the innervation pattern and morphogenesis of the oral lip papillae in the onychophoran Euperipatoides rowelli using DNA labeling, immunocytochemistry, and neuronal tracing techniques. Our morphogenetic data revealed that the seven paired and one unpaired oral lip papillae arise from three anterior-most body segments. Retrograde fills show that only the first and the third nerves supplying the lip papillae are associated with cell bodies within the brain, whereas the second nerve exclusively receives fibers from somata of peripheral neurons located in the lip papillae. According to our anterograde fills and immunocytochemical data, the first nerve supplies the anterior-most pair of lip papillae, whereas the second and the third nerves are associated with the second to fifth and second to eighth lip papillae, respectively. These data suggest that the lip papillae of E. rowelli are mainly innervated by the proto- and deutocerebrum, whereas there are only a few additional cell bodies situated posterior to the brain. According to these findings, the overall innervation pattern of the oral lip papillae in E. rowelli is incompatible with the interpretation of the onychophoran brain as a modified circumoral ring.

No description available.

No description available.

No description available.

The speech of an individual conveys a great deal of information about how their central nervous system (CNS) is performing. Whether they are tired, distressed or suffering from a degenerative disease affecting the brainstem, speech can change as a function of an individual’s condition. Yet, when assessing the speech in an individual on the first occasion, it is often difficult to determine whether their performance is different from a pre-morbid level. Therefore, the repeated acquisition and analysis of a set of brief and simple speech measures could provide information on changes in a patient’s performance over time. This could ultimately lead to the inclusion of objective markers of change in trials of conditions and disorders that currently rely of subjective, clinician derived measures of severity or patient self report, such as pain, depression or fatigue. Furthermore, the information could be used to track patient performance in treatment trials for degenerative disorders, such as Friedreich ataxia or Huntington’s disease. / This thesis aimed to evaluate the practical, experimental and statistical requirements of speech assessment protocols designed to monitor patient performance over time. The research involved a number of studies evaluating methods for acquiring and analysing data, studies examining the stability and sensitivity of speech stimuli, and finally, the functionality of these findings in an experimental model known to induce change in CNS function (i.e., sustained wakefulness). / Methods for acquiring and analysing speech data were designed to provide a balance between the concurrent demands for precision and useability inherent in repeated assessment protocols. Data from these studies provided evidence that techniques offering high levels of useability (e.g., easy to use, automated) are capable of offering adequate precision on broad acoustic measures of timing and frequency. Moreover, these methods could be standardised and automated, allowing non-expert users to collect and analyse data in a controlled and time efficient manner. The second series of experiments systematically documented the stability and responsiveness of speech stimuli within a variety of experimental conditions. These studies were designed to establish the suitability of select speech measures for monitoring change in individuals over time, as stimuli that proved to be both stable (across several re-test intervals) and sensitive to change or impairment were ideal candidates. Finally, a proof of concept study designed to evaluate the efficiency and sensitivity of the proposed methodology was initiated in an experimental model known to induce changes in psychomotor functioning in healthy adults (sustained wakefulness). Significant changes from baseline were observed in speech production as a function of increasing levels of fatigue. These findings are important as they demonstrate the potential of speech as a valid, reliable and sensitive marker of change in conditions where the CNS is subject to stress.

The speech of an individual conveys a great deal of information about how their central nervous system (CNS) is performing. Whether they are tired, distressed or suffering from a degenerative disease affecting the brainstem, speech can change as a function of an individual’s condition. Yet, when assessing the speech in an individual on the first occasion, it is often difficult to determine whether their performance is different from a pre-morbid level. Therefore, the repeated acquisition and analysis of a set of brief and simple speech measures could provide information on changes in a patient’s performance over time. This could ultimately lead to the inclusion of objective markers of change in trials of conditions and disorders that currently rely of subjective, clinician derived measures of severity or patient self report, such as pain, depression or fatigue. Furthermore, the information could be used to track patient performance in treatment trials for degenerative disorders, such as Friedreich ataxia or Huntington’s disease. / This thesis aimed to evaluate the practical, experimental and statistical requirements of speech assessment protocols designed to monitor patient performance over time. The research involved a number of studies evaluating methods for acquiring and analysing data, studies examining the stability and sensitivity of speech stimuli, and finally, the functionality of these findings in an experimental model known to induce change in CNS function (i.e., sustained wakefulness). / Methods for acquiring and analysing speech data were designed to provide a balance between the concurrent demands for precision and useability inherent in repeated assessment protocols. Data from these studies provided evidence that techniques offering high levels of useability (e.g., easy to use, automated) are capable of offering adequate precision on broad acoustic measures of timing and frequency. Moreover, these methods could be standardised and automated, allowing non-expert users to collect and analyse data in a controlled and time efficient manner. The second series of experiments systematically documented the stability and responsiveness of speech stimuli within a variety of experimental conditions. These studies were designed to establish the suitability of select speech measures for monitoring change in individuals over time, as stimuli that proved to be both stable (across several re-test intervals) and sensitive to change or impairment were ideal candidates. Finally, a proof of concept study designed to evaluate the efficiency and sensitivity of the proposed methodology was initiated in an experimental model known to induce changes in psychomotor functioning in healthy adults (sustained wakefulness). Significant changes from baseline were observed in speech production as a function of increasing levels of fatigue. These findings are important as they demonstrate the potential of speech as a valid, reliable and sensitive marker of change in conditions where the CNS is subject to stress.

Thesis (Ph.D.)--Tufts University, 1998. / Adviser: Barry A. Trimmer. Submitted to the Dept. of Biology. Includes bibliographical references (leaves 92-105). Access restricted to members of the Tufts University community. Also available via the World Wide Web;