Effects of HZE Irradiation on Chemical Neurotransmission in Rodent Hippocampus

<p>Space radiation represents a significant risk to the CNS (central nervous system) during space missions. Most harmful are the HZE (high mass, highly charged (Z), high energy) particles, e.g. ⁵⁶Fe, which possess high ionizing ability, dense energy deposition pattern, and high penetrance.</p> <p>Accumulating evidence suggests that radiation has significant impact on cognitive functions. In ground-base experiments, HZE radiation induces pronounced deficits in hippocampus dependent learning and memory in rodents. However, the mechanisms underlying these impairments are mostly unknown.</p> <p>Exposure to HZE radiation elevates the level of oxidation, resulting in cell loss, tissue damage and functional deficits through direct ionization and generation of reactive oxygen species (ROS). When hippocampal slices were exposed to ROS, neuronal excitability was reduced. My preliminary results showed enhanced radio-vulnerability of the hippocampus and reduction in basal and depolarization-evoked [³H]-norepinephrine release after HZE exposure. These results raised the possibility that HZE radiation deteriorates cognitive function through radiation-induced impairments in hippocampal chemical neurotransmission, the hypothesis of this dissertation.</p> <p>In Aim 1 I have focused on the effects of HZE radiation on release of major neurotransmitter systems in the hippocampus. I have further extended my research on the levels of receptors of these systems in Aim 2. In Aim 3, I have studied the level of oxidation in membranes of my samples.</p> <p>My research reveals that HZE radiation significantly reduces hyperosmotic sucrose evoked [3H]-glutamate and [14C]-GABA release both three and six months post irradiation. The same radiation regimen also significantly enhances oxidative stress as indicated by increased levels of lipid peroxidation in the hippocampus, suggesting that increased levels of lipid peroxidation may play a role in reduction of neurotransmitter release. HZE radiation also significantly reduces levels of neurotransmitter receptors critical to synaptic plasticity; glutamatergic NMDA (<em>N</em>-methyl <em>D</em>-aspartate) receptors and β1 adrenergic receptors, three months post irradiation. By six months post irradiation, the levels of these receptors are returned to normal, implying that partial repair may take place.</p> <p>My findings demonstrate that a single dose of HZE radiation alters the neurochemical environment in the hippocampus, which may underlie radiation-induced cognitive dysfunction.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Year dc:date.available

2009

Author dc:creator

• Machida, Mayumi

Contributors dc:contributor

• Gyorgy Lonart
• Richard A. Britten
• Laura K. Hanson
• Larry D. Sanford

• HZE particles
• Hippocampus
• Irradiation
• Neurotransmission
• Reactive oxygen species
• Space radiation
• Neuroscience and Neurobiology
• Nuclear

Identifier

9781109217544

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biomedicalsciences_etds-1056