Using a the SERCaMP technology that we previously developed, we show that both a cafeteria diet and high fat diet cause ER calcium dysfunction in rat liver. The dysregulation of ER calcium is implicated in wide variety of disease states. Our findings provide a possible mechanism by which liver function is altered in response to excessive fat in the diet. Our findings our published in the Journal of Hepatology. We describe the characterization and development of multiple transgenic tools that express a near-infrared fluorescent protein (IRFP) in neurons as a reporter of transgene expression. The longer wavelength of light used for visualization offers many advantages over other fluorescent reporters used for neuroscience applications related to understanding the cellular basis of addiction. This work was published in J Neuroscience Methods. In collaboration with Geoffrey Schoenbaum (NIDA) and Marisela Morales (NIDA), we developed a transgenic rat that selectively expresses Cre-recombinase in the GABAergic neurons. Using the rat, they were able to show how GABAergic neurons in the lateral hypothalamus encode reward predictions related to learning. This transgenic rat has been requested by over 50 laboratories world-wide. This work was published in Current Biology. In collaboration Yavin Shaham (NIDA) we examined the role of histone deacetylase 5 expression in the dorsal striatum on the incubation of methamphetamine craving. this work is published in Biological Psychiatry. In collaboration with Mike Michaelides (NIDA) we found that clozapine is the active ligand for DREADDS. This work is published in Science. In collaboration with Drs. Koob and Leggio, we developed and characterized a ghrelin receptor knockout rat. This work is published in Int J Obes (London). In collaboration with Dr. Mikko Airavaara we discovered that naloxone and its enantiomer can be administered intranasally post-ischemia to a rat to reduce inflammation and improve recovery in a rodent model of stroke. This work is published in eNeuro. In collaboration with Dr. Bruce Hope, we expolored parameters of microspheres that help mediated their internalization into neurons. This work is published in Cell Mol Neurobiol.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2018
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
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Type
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Anttila, Jenni E; Albert, Katrina; Wires, Emily S et al. (2018) Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury. eNeuro 5:
Zallar, L J; Tunstall, B J; Richie, C T et al. (2018) Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model. Int J Obes (Lond) :
Li, Xuan; Carreria, Maria B; Witonsky, Kailyn R et al. (2018) Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving. Biol Psychiatry 84:213-222
Wallace, Veronica J; Cimbro, Raffaello; Rubio, F Javier et al. (2017) Neurons Internalize Functionalized Micron-Sized Silicon Dioxide Microspheres. Cell Mol Neurobiol 37:1487-1499
Koskela, Maryna; Bäck, Susanne; Võikar, Vootele et al. (2017) Update of neurotrophic factors in neurobiology of addiction and future directions. Neurobiol Dis 97:189-200
Sharpe, Melissa J; Marchant, Nathan J; Whitaker, Leslie R et al. (2017) Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning. Curr Biol 27:2089-2100.e5
Gomez, Juan L; Bonaventura, Jordi; Lesniak, Wojciech et al. (2017) Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 357:503-507
Wires, Emily S; Trychta, Kathleen A; Bäck, Susanne et al. (2017) High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver. J Hepatol 67:1009-1017
Wires, Emily S; Henderson, Mark J; Yan, Xiaokang et al. (2017) Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo. PLoS One 12:e0175481
Richie, Christopher T; Whitaker, Leslie R; Whitaker, Keith W et al. (2017) Near-infrared fluorescent protein iRFP713 as a reporter protein for optogenetic vectors, a transgenic Cre-reporter rat, and other neuronal studies. J Neurosci Methods 284:1-14

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