Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Casey Paton - Fisk University
Co-Author(s): Ke'ara Brown-Smith, Fisk University
Dopamine is a neurotransmitter synthesized in the substantia nigra and ventral tegmental areas of the brain. Dopamine is involved in motor control, reward pathways, pleasure, and addiction; misregulation of dopamine signaling is associated with conditions such as Parkinson’s disease, schizophrenia, and ADHD. High levels of manganese have been shown to cause motor deficits similar to those exhibited in Parkinson’s disease (1). Manganese is known to accumulate in the basal ganglia of the brain but a complete mechanism of manganese neurotoxicity has yet to be elucidated (2).
Earlier research in our lab showed that Caenorhabditis elegans lacking the novel transcription factor Forkhead Eight (fkh-8), treated for thirty minutes with 50mM or 100mM MnCl2 exhibited increased neurodegeneration (shown by blebbing and loss of GFP fluorescence in CEP neurons). We are considering regulation of the genes encoding the SMF-1 and SMF-2 manganese transporters by FKH-8 as a potential source of this mechanism; is the increased sensitivity to manganese-induced neurodegeneration seen in fkh-8 mutants occurring through changes in the amount or activity of the SMF-1 or SMF-2 manganese transporters? I will cross strains to engineer fkh-8; smf-1 and fkh-8; smf-2 double mutant worms to test if the neurodegeneration caused by MnCl2 treatment differs between wildtype worms and these mutants lacking the SMF transporter. If so, this would suggest the SMF-1 or SMF-2 manganese transporters are altered upon loss of FKH-8, which leads to subsequent exacerbation of CEP neuron degeneration. This research is important to characterize the molecular aspects and transcriptional regulation of manganese toxicity and dopaminergic control. Such knowledge is critical to understand proper neuronal function and to develop treatments for Parkinson’s disease, Schizophrenia, and ADHD.
References: 1. Dobson, A. W., Erikson, K. M. and Aschner, M. (2004), Manganese Neurotoxicity. Annals of the New York Academy of Sciences, 1012: 115–128. doi: 10.1196/annals.1306.009. 2. Fitsanakis, V.A., Au, Catherine, Erikson, K.M., Aschner, M. (2006) The effects of manganese on glutamate, γ- aminobutyric acid, and dopamine regulation. Neurochem. Intl. 48(6-7): 426-433.Casey Paton- ERNC Abstract.docx
Funder Acknowledgement(s): NSF grant #1500320, Tennessee LSAMP Bridge to the Doctorate Program at Vanderbilt University
Faculty Advisor: Brian Nelms, email@example.com