This core will provide Biophysical based assessments for CHAIN investigators. Both state-of-the-art Bioimaging, including quantitative magnetic resonance imaging (MRI), MR spectroscopy (MRS) and single photon emission computed tomography (SPECT), and Electrophysiological methods, including patch clamping and extracellular analysis synaptic activity. Two 7-Tesla small animal MRl/S systems will provide quantitative neuroimaging and/or superparamagnetic iron oxide (SPIO) labeled cell tracking on rodent models of HlV-1 associated neurodegenerative disorder (HAND). The bioimaging core methods also include quantitative mapping of blood-brain barrier permeability, quantitative arterial spin labeled perfusion mapping, and quantitative proton MRS (^H MRS). The electrophysiology equipment and expertise will allow investigators access to state-of-the-art in vitro and in vivo approaches for studying how immune deficiency virus, viral products, cytokines, and cytotoxins, as well as genetic over- or under-expression of these elements alter molecular, cellular and synaptic physiology of neurons and brain regions believed to be involved in neuroAIDS. The techniques in the Core as a whole will also support developmental therapeutic studies relevant to microglial activation in HAD. The results obtained from this core will have direct applicability for determining the mechanisms and monitoring the course of HIV infection in its chronic stage. Our overriding goal is to assist CHAIN Pis and other researchers interested in neuroAIDS in determining and characterizing changes of CNS function as they develop in the various in vitro and in vivo models of neuroAIDS, and in exploring therapeutic potentials aiming at ameliorating or reversing such functional changes.

Public Health Relevance

Interdisciplinary studies are key to the analysis of complex diseases such as HIV infection of the brain. This core will enable CHAIN scientists from a variety of fields to access state-of-the-art bioimaging and neurophysiological technoligies to meet the aims ofthe Center.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Center Core Grants (P30)
Project #
5P30MH062261-14
Application #
8629783
Study Section
Special Emphasis Panel (ZMH1-ERB-M)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
14
Fiscal Year
2014
Total Cost
$211,075
Indirect Cost
$68,937
Name
University of Nebraska Medical Center
Department
Type
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
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Stauch, Kelly L; Emanuel, Katy; Lamberty, Benjamin G et al. (2017) Central nervous system-penetrating antiretrovirals impair energetic reserve in striatal nerve terminals. J Neurovirol 23:795-807
Li, Weizhe; Gorantla, Santhi; Gendelman, Howard E et al. (2017) Systemic HIV-1 infection produces a unique glial footprint in humanized mouse brains. Dis Model Mech 10:1489-1502
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Sandkovsky, Uriel; Podany, Anthony T; Fletcher, Courtney V et al. (2017) Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. J Antimicrob Chemother 72:200-204
Gnanadhas, Divya Prakash; Dash, Prasanta K; Sillman, Brady et al. (2017) Autophagy facilitates macrophage depots of sustained-release nanoformulated antiretroviral drugs. J Clin Invest 127:857-873
Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn et al. (2017) Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis. Nanomedicine (Lond) 12:99-115
Edagwa, Benson; McMillan, JoEllyn; Sillman, Brady et al. (2017) Long-acting slow effective release antiretroviral therapy. Expert Opin Drug Deliv 14:1281-1291
Guo, Dongwei; Zhou, Tian; Araínga, Mariluz et al. (2017) Creation of a Long-Acting Nanoformulated 2',3'-Dideoxy-3'-Thiacytidine. J Acquir Immune Defic Syndr 74:e75-e83

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