NATE HODGSON AND GIRISH CHOPDA
Nate Hodgson and Girish Chopda won the Outstanding Student Research Awards at the 2010 Northeastern University Research Expo
Nate Hodgson is a doctoral student working under Professor Richard Deth. Nate’s project is titled“EAAT3-Mediated Cysteine Uptake in Human Neuroblastoma Cells is PI3 Kinase-Dependent”.
The concentration of intracellular cysteine is rate-limiting for synthesis of glutathione (GSH), the major cellular anti-oxidant. Factors regulating cysteine uptake can therefore exert a powerful influence over cellular redox status. This is particularly the case when de novo cysteine synthesis via transulfuration of homocysteine is restricted, as is the case in adult human neurons. In mature neurons the primary pathway for uptake of cysteine is provided by excitatory amino acid transporter 3 (EAAT3). The depletion of GSH associated with oxidative stress has been linked to neurodevelopmental and neurodegenerative disorders such as autism, Alzheimer’s and Parkinson’s diseases. Due to the importance of EAAT3 in providing cysteine for the cell’s redox machinery, the regulation of EAAT3 by growth factors was studied. Nate’s findings show that IGF-1, and GDNF, increased cysteine transport which was inhibited by PI3-kinase inhibitors. The current studies suggest that PI3-kinase exerts its effects at the level of EAAT3, by modulating cellular thiol levels and their redox state. Taken together these results illustrate a novel mechanism by which growth factor signaling can exert control over cellular redox status, via an influence over EAAT3-mediated cysteine uptake.
Girish R Chopda is a doctoral student working under Professor Carol Paronis. Girish’s project is titled “Effects of CB1 Cannabinoid Agonists in Rats”
Cannabis and related plant-derived compounds are used by some patient populations to alleviate pain and nausea. In addition to this ongoing use, cannabinoid (CB) compounds have been proposed to have potential therapeutic uses for a broad range of central nervous system, cardiovascular, and gastrointestinal diseases. However, the broad acceptance of cannabinoids as medications has been tempered by their undesirable psychoactive effects and their unpredictable pharmacokinetic effects. To address the latter problem, a series of compounds have been synthesized by the center for drug discovery (CDD) at Northeastern University. These compounds are proposed to have similar pharmacodynamic profiles as Δ9-tetrahydrocannabinol (THC), the prototypic cannabinoid, but with quicker onsets and shorter durations of action. The present studies sought to characterize these novel compounds according to their behavioral effects in comparison to a potent CB1 agonist. Previous studies of the behavioral effects of novel cannabinoid ligands have often relied on a tetrad of tests – locomotor activity, hypothermia, antinociception, and immobility; however a hall mark of this tetrad is that drugs that act as agonists at CB1 receptors are predicted to produce similar results across the four measures. In an effort to develop assays that are more sensitive to differences between drugs, we have employed one of the tetrad assays, hypothermia, to provide a measure of comparability to results obtained in other studies, and two other measures of CB effects in an effort to characterize differences between drugs. First, we assessed the ability of drugs to increase diuresis, an effect that has previously been shown to be CB1 receptor mediated. Second, we assessed the ability of drugs to decrease operant responding, a behavioral effect of drugs that is often seen at doses lower than those required to produce physiological effects.