The etiology of bipolar disorder (BD) is multidimensional and thought to involve several factors that increase neuronal oxidative stress and disrupt intracellular calcium homeostasis. As calcium-permeable canonical transient receptor potential channels (TRPC) have been linked to bipolar pathophysiology, I sought to determine whether oxidative stress affects TRPC3/TRPC5/TRPC6 expression and/or function. Chronic (4-day) but not acute (24-hour) rotenone-induced oxidative stress dose-dependently reduced TRPC5 and TRPC6 protein levels in primary rat cortical neurons. A decrease in TRPC5 mRNA levels was only found following acute but not chronic rotenone whereas TRPC6 mRNA levels did not change significantly with either treatment. Reduced TRPC3 function was seen after chronic stress when stimulated by TRPC3/6 activator, 1-oleoyl-2-acetyl-sn-glycerol. Lithium pre-treatment attenuated the rotenone-induced reduction in TRPC3 but not TRPC6 protein levels. These results suggest TRPC subtypes are differentially regulated by oxidative stress and support a potential mechanistic link between oxidative stress and calcium dyshomeostasis in BD.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32495 |
| Date | 23 July 2012 |
| Creators | Tong, Steven |
| Contributors | Warsh, Jerry |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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