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 studies in this project is to obtain in vivo confirmation of the potential antiparkinsonian effects of blockade of NR2D-type NMDA receptors in an animal model of Parkinson's disease, the 6-OH-dopamine-lesioned rat. These agents are most likely to work by blocking NR2D receptors in the subthalamic nucleus, a structure which is overactive in Parkinson's disease. NR2D receptor blockade may act to normalize the activity in this nucleus. To test this hypothesis, three experiments were planned: (1) To establish the concentration-effect curve for inhibition of native NR2D-containing NMDA receptors in subthalamic neurons by our best NR2D-selective antagonist. The combination of this data with in vivo pharmacokinetic data will allow us to estimate receptor occupancy as a function of administered dose. (2) To determine the NR2D protein distribution using immunohistochemistry in normal rats and rats treated with 6-OH-dopamine to confirm that NR2D receptors are present in this animal model of Parkinson's disease. (3) To evaluate the ability of selective blockade of NR2D-containing receptors in basal ganglia neurons to alter motor behavior in 6-OHDA-lesioned animals. This project was completed and publications of results are in preparation.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000165-51
Application #
8357477
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-08-01
Project End
2012-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
51
Fiscal Year
2011
Total Cost
$32,906
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Maddox, S A; Kilaru, V; Shin, J et al. (2017) Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Mol Psychiatry :
Banerjee, Sunayana B; Gutzeit, Vanessa A; Baman, Justin et al. (2017) Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning. Neuron 95:169-179.e3
Bruner, Emiliano; Preuss, Todd M; Chen, Xu et al. (2017) Evidence for expansion of the precuneus in human evolution. Brain Struct Funct 222:1053-1060
Chen, Guiqin; Nie, Shuke; Han, Chao et al. (2017) Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats. Front Neurosci 11:112
Dehkharghani, S; Fleischer, C C; Qiu, D et al. (2017) Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke. AJNR Am J Neuroradiol 38:712-720
Walker, Lary C; Jucker, Mathias (2017) The Exceptional Vulnerability of Humans to Alzheimer's Disease. Trends Mol Med 23:534-545
Payne, Christa; Cirilli, Laetitia; Bachevalier, Jocelyne (2017) An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions. Dev Psychobiol 59:495-506
Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev et al. (2017) CD4(+) Foxp3(+) T cells promote aberrant immunoglobulin G production and maintain CD8(+) T-cell suppression during chronic liver disease. Hepatology 65:661-677
Hecht, E E; Mahovetz, L M; Preuss, T M et al. (2017) A neuroanatomical predictor of mirror self-recognition in chimpanzees. Soc Cogn Affect Neurosci 12:37-48
Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena et al. (2017) A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice. Vaccine 35:3239-3248

Showing the most recent 10 out of 880 publications