Our overall aim is to understand the molecular events that underlie glutamate receptor mediated signal transduction in the brain. In particular, we have studied the effect of glutamate receptor activation on the concentration of neuronal Ca, (Ca)i, and resulting effects on the state of neuronal mitochondria and the production of superoxide and other reactive oxygen species (ROS). In the present proposal we shall be interested in understanding how these events may be involved in glutamate receptor mediated excitotoxic neuronal degeneration, a process that is believed to be extremely important in many types of neurodegenerative diseases including stroke and epilepsy. We shall use imaging procedures to examine how the activation of glutamate receptors in the brain can regulate the state of mitochondria and the production of ROS and how these processes are regulated. We shall also be interested in how these processes can be altered by activation of the metabotropic glutamate receptors that are also stimulated by synaptically released glutamate. We shall further investigate the importance of Ca and ROS by manipulating the concentrations of key neuronal proteins such as superoxide dismutase and nitric oxide synthase using an adenovirus expression system. Overall we hope that these studies will increase our understanding of glutamate mediated signal transduction in the brain and its role in neurodegenerative disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH040165-15
Application #
2890331
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Program Officer
Asanuma, Chiiko
Project Start
1985-06-01
Project End
2003-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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White, Fletcher A; Miller, Richard J (2010) Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain. Brain Behav Immun 24:859-65
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Jung, Hosung; Miller, Richard J (2008) Activation of the nuclear factor of activated T-cells (NFAT) mediates upregulation of CCR2 chemokine receptors in dorsal root ganglion (DRG) neurons: a possible mechanism for activity-dependent transcription in DRG neurons in association with neuropathic Mol Cell Neurosci 37:170-7
Jung, Hosung; Toth, Peter T; White, Fletcher A et al. (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104:254-63

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