Year: 2007
Type: dissertation
Abstract: The organic or methylated form of mercury (Hg), consisting of one methyl group\nbound to each atom of Hg, (methylmercury; MeHg), accounts for most of the Hg to\nwhich humans are exposed. MeHg, by virtue of its lipophilicity is highly neurotoxic to\nboth the developing and mature central nervous system (CNS). Historically, MeHg has\nbeen implicated in high morbidity and mortality rates over the last 40 years in Japan,\nIraq, Pakistan and Guatemala. The most common symptom exhibited in these exposure\nepisodes was cerebellar ataxia. Recent in vitro studies using cultured granule cells\nshowed that MeHg alters intracellular calcium ion ([Ca2+]i) homeostasis, potentiates\nreactive oxygen species (ROS) generation and loss of mitochondrial membrane potential\nleading to apoptotic death of cerebellar granule neurons. To better understand the\nneurotoxic mechanisms of MeHg on cerebellum, changes with respect to biochemical\nprocesses in cerebellar granule cells and associated behavior changes were investigated.\nThe aims of this dissertation were: (1) to assess mercury concentrations in mouse\nbrain using different routes of administration and different tissue preparations, (2) to\ndetermine the behavior effects of in vivo MeHg exposure in young adult mice. (3) to understand specific biochemical processes leading to granule cell death/dysfunction due\nto in vivo MeHg toxicity in mice, and (4) to determine the toxic effects of in vivo MeHg\nexposure on mice aged between 16-20 months.\nThe present results showed that repeated oral exposure to MeHg results in greater\naccumulation of Hg in brain tissue when compared to single oral or subcutaneous\nexposures at the same concentration of MeHg. Behavior analysis revealed that MeHg at\nthe concentrations used in this study had profound effects on motor coordination and\nbalance in young adult and aged mice. Investigation of biochemical processes in\ncerebellar granule cells of mice exposed to MeHg showed an increase in ROS\ngeneration, alteration of ([Ca2+]i (in young adult mice) and loss of MMP in young adult\nand aged mice. However, these changes did not lead to apoptotic cell death of granule\ncells at the concentrations of MeHg used and at the specific time point it was\ninvestigated in young adult mice.
Author: Sairam Bellum
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Funder: National Institutes of Health
Award: G2198807715
OpenAlex ID: W2289348618