Research
Neuroscience, Neurotoxicology and Neuroethology
The major thrust of the lab is to examine the effects of copper on the behavior and neural function of the aquatic oligochaete worm Lumbriculus variegatus. We are using this system as a model for human neurodegenerative diseases. There is a growing realization that copper-induced toxicity plays a role in many pathological conditions where derangements of the ability to regulate copper levels are not considered the primary cause. Elevated levels of copper occur within the nervous system during neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and spongiform encephalopathies (such as mad cow disease). There are other conditions where derangements in copper homeostasis are the primary cause of neurodegeneration, often producing Parkinsonian symptomatology. These conditions include Wilson's disease, chronic liver failure, and environmental exposure to copper (such as occurs in copper miners or smelters). Our goal is to protect the nervous system of Lumbriculus from the toxic effects of copper. If we are successful, similar treatments may be able to reduce the severity and progression of human neurodegenerative diseases.
We have examined the effects of copper exposure on two touch-evoked behaviors: helical swimming, and body position reversal as well as spontaneous crawling behavior. Copper exposure detrimentally affects each of these locomotor behaviors. In addition, we use noninvasive techniques to monitor the electrophysiological activity of giant neurons and muscles that produce rapid escape responses. Copper exposure reduces the speed at which neural signals propagate along the giant neurons. Much of our current research activities center on determining exactly what aspects of neural function are altered by copper exposure. We have determined that each of the above behaviors is dependent up the amine neurotransmitters (dopamine, serotonin, octopamine, and histamine), and that the different behaviors are dependent upon different amines. We hope to tie copper-induced deficits to damage induced in neurons using these neurotransmitters.
We have been able to protect the worms from some of the toxic actions of copper exposure using the vitamin E analog Trolox. However, we also found that Trolox produces toxic actions of its own. This is one of the few published reports showing toxicity from vitamin E or one of its derivatives.
Recent graduate student projects
- Kathryn Hedges examined the effects of copper exposure on dopaminergic and GABAnergic neurons in the nematode Caenorhabditis elegans. Kathryn's work involved image analysis of worms expressing green fluorescent protein (GFP) in identified neurons. Using the live/dead fluorescent dye SYTOX Orange, Kathryn was also able to show that copper exposure paralyzed worms at concentrations far below lethal concentrations.
- Jamey Krauss examined the effects of the neuropeptide FMRFamide on a region of the earthworm gut called the crop-gizzard. A major thrust of Jamey's work examined the transduction mechanisms underlying the FMRFamide-induced responses. Jamey determined that the phosphatidylinositol and arachidonic acid second messenger pathways were vitally important in mediating FMRFamide's effects on the crop-gizzard.
- Philip Cramer evaluated transgenic Caenorhabditis elegans as bioindicators for the presence of toxins in the environment. Each strain had Green Fluorescent Protein (GFP) production linked to the promoter region of a gene known to be involved in either the stress response, metabolism, or development. The results indicated that single-gene biomarker-based bioassays can only be used in limited situations with particular toxins.