This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Physiological activation of MNDA receptors (NMDARs) plays a critical role in synaptic plasticity and neuronal survival. Exessive activation of NMDARs on the other hand has been implicated in mediating neurodegeneration following ischemia and traumatic brain injury (TBI). Although many studies have shown promising neuroprotective properties for NMDAR antagonists in experimental models of Stroke and TBI, clinical trials using such antagonists have failed. The issue at hand is to separate the positive benefits of NMDAR activation from the negative ones. The hypothesis driving the proposed research is that SynGAP (synaptic Ras GRPase activating protein) serves as a regulatory switch controlling NMDAR-mediated activation of both pro-survival and pro-death signaling.
The specific aims, which include 1) Determining the functional protein domain(s), which mediate SynGAP's role in NMDAR-mediated excitotoxicity and 2) establishing a protocol to selectively knockdown SynGAP expression in vitro using RNAi, are created to provide an assessment of SynGAP's role in regulating NMDAR-mediated cell death in vitro and identify a strategy for the development of potential therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015567-10
Application #
7959611
Study Section
Special Emphasis Panel (ZRR1-RI-8 (02))
Project Start
2009-06-01
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
10
Fiscal Year
2009
Total Cost
$12,392
Indirect Cost
Name
University of South Dakota
Department
Neurosciences
Type
Schools of Medicine
DUNS #
929930808
City
Vermillion
State
SD
Country
United States
Zip Code
57069
Burrell, Brian D (2017) Comparative biology of pain: What invertebrates can tell us about how nociception works. J Neurophysiol 117:1461-1473
Robertson, James M; Achua, Justin K; Smith, Justin P et al. (2017) Anxious behavior induces elevated hippocampal Cb2 receptor gene expression. Neuroscience 352:273-284
Novick, Andrew M; Mears, Mackenzie; Forster, Gina L et al. (2016) Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood. Behav Brain Res 304:51-9
Smith, Justin P; Prince, Melissa A; Achua, Justin K et al. (2016) Intensity of anxiety is modified via complex integrative stress circuitries. Psychoneuroendocrinology 63:351-61
Ranek, Mark J; Zheng, Hanqiao; Huang, Wei et al. (2015) Genetically induced moderate inhibition of 20S proteasomes in cardiomyocytes facilitates heart failure in mice during systolic overload. J Mol Cell Cardiol 85:273-81
Hahn, Elizabeth; Burrell, Brian (2015) Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech. Invert Neurosci 15:177
Novick, Andrew M; Forster, Gina L; Hassell, James E et al. (2015) Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress. Neuropharmacology 97:194-200
Robertson, James M; Prince, Melissa A; Achua, Justin K et al. (2015) Nuance and behavioral cogency: How the Visible Burrow System inspired the Stress-Alternatives Model and conceptualization of the continuum of anxiety. Physiol Behav 146:86-97
Ranek, Mark J; Kost Jr, Curtis K; Hu, Chengjun et al. (2014) Muscarinic 2 receptors modulate cardiac proteasome function in a protein kinase G-dependent manner. J Mol Cell Cardiol 69:43-51
Watt, Michael J; Roberts, Christina L; Scholl, Jamie L et al. (2014) Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors. Psychopharmacology (Berl) 231:1627-36

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