This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the proposed research is to develop and use models of modest excitotoxic hippocampal injury to assess the cognitive enhancing ability of specific candidate compounds. Our preliminary data demonstrate that excitotoxic injury to the dorsal hippocampus produces enduring deficits in spatial working memory. We have also shown in preliminary studies that antagonists at histamine H3 receptors alleviate injury-induced deficits in spatial working memory.
The specific aims of our currently-funded R15 research have been to answer the following questions: 1) Can H3 antagonists alleviate spatial working memory deficits in rats with adult-onset hippocampal injury, 2) Can direct infusion of H3 antagonists into the prefrontal cortex improve memory in rats with adult-onset hippocampal injury, &3) Can H3 antagonists alleviate changes in spatial working memory, prepulse inhibition, and locomotor activity in rats with neonatal-onset hippocampal injury? For this application, we requested INBRE supplemental support for a research associate who can advance the aims of our R15 research and supervise undergraduate research. Between May 2009 and the present, we have assessed the effects of H3 antagonists on spatial memory deficits and other behavioral anomalies produced by drugs that block NMDA receptors. These studies, mainly performed by Molly Griffith, our research associate, and several undergraduates in the lab, have shown that H3 antagonists exacerbate the effects of NMDA antagonists on locomotor activity, but also alleviate the spatial memory deficits produced by such drugs. We submitted an R15 to continue these studies in June 2009 and it received a priority score of 37. We will revise and resubmit this application in February 2010. Having INBRE support for our research associate has greatly facilitated the pace of our R15 research and resulted in two published papers, support for award-winning undergraduate research, and an R15 renewal application that received a favorable (although unfundable) score.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Louisville
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Hofmann, Emily; Webster, Jonathan; Do, Thuy et al. (2016) Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers. Bioorg Med Chem 24:578-87
Rau, Kristofer K; Hill, Caitlin E; Harrison, Benjamin J et al. (2016) Cutaneous tissue damage induces long-lasting nociceptive sensitization and regulation of cellular stress- and nerve injury-associated genes in sensory neurons. Exp Neurol 283:413-27
Rouchka, Eric C; Flight, Robert M; Fasciotto, Brigitte H et al. (2016) Transcriptional profile of immediate response to ionizing radiation exposure. Genom Data 7:82-5
Smith, Michael E; Monroe, J David (2016) Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes. Adv Exp Med Biol 877:393-417
Harrison, Benjamin J; Venkat, Gayathri; Lamb, James L et al. (2016) The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity. J Neurosci 36:4259-75
Saikkonen, Kari; Young, Carolyn A; Helander, Marjo et al. (2016) Endophytic Epichloë species and their grass hosts: from evolution to applications. Plant Mol Biol 90:665-75
Hestand, Matthew S; Kalbfleisch, Theodore S; Coleman, Stephen J et al. (2015) Annotation of the Protein Coding Regions of the Equine Genome. PLoS One 10:e0124375
Young, Carolyn A; Schardl, Christopher L; Panaccione, Daniel G et al. (2015) Genetics, genomics and evolution of ergot alkaloid diversity. Toxins (Basel) 7:1273-302
Harrison, Benjamin J; Venkat, Gayathri; Hutson, Thomas et al. (2015) Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model. Genom Data 6:249-52
Stenslik, Mallory J; Potts, Lisa F; Sonne, James W H et al. (2015) Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease. J Neurosci Methods 251:120-9

Showing the most recent 10 out of 239 publications