OVERALL ABSTRACT The use of antiretroviral therapy to turn HIV infection into a chronic disease has been a major medical advancement. However, along with this has been the recognition of sequelae of HIV as a chronic condition, with end-organ consequences such as the HIV-associated neurocognitive disorder (HAND), as the brain is a target of HIV, and interactions with disease associated with aging. Indeed, the face of HIV infection is changing to an older population, and soon over half of infected individuals in the U.S. will be 50 years of age or greater. As age is the largest risk factor for neurodegenerative diseases, this graying of the HIV pandemic is a critical focus of study especially for the central nervous system. Furthermore, the brain can provide a reservoir for HIV, impacting efforts to find a functional cure. NIH P30 Centers support shared resources and facilities for research in a focused field. Here, we propose to build upon striking successes we have made in multiple areas to continue the UNMC Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center. We have revised the Center based on our findings and current issues and needs in the field, and these closely follow the new NIH priority topics for using AIDS-designated funds, including neurological complications, comorbidies, cross-cutting basic research, long-acting therapeutics, and reservoir and cure. Through this Center mechanism, we will significantly facilitate research and accomplishments across these areas. Experts in a number of fields will direct Imaging, Therapeutics, Cell- Tissue-Animal, and Omics Cores. These, combined with a Developmental Core to stimulate new and innovative work and an Administrative Core to integrate and run the Center, will serve to significantly enhance our knowledge of neuroAIDS, its prevention and treatment, while joining others in work for an overall cure for HIV.

Public Health Relevance

While HIV infected individuals are living longer due to treatment, effects on the central nervous system persist. Furthermore, as age is the highest risk factor for neurodegenerative diseases, knowledge of the effects of HIV and aging on the brain is critical. The brain can also provide a reservoir for the virus, hampering efforts towards a cure. Our Center will be a resource for investigators to diagnose, treat, prevent, and hopefully cure these consequences of HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Center Core Grants (P30)
Project #
5P30MH062261-18
Application #
9669117
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Joseph, Jeymohan
Project Start
2000-09-30
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
18
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Olson, Katherine E; Bade, Aditya N; Namminga, Krista L et al. (2018) Persistent EcoHIV infection induces nigral degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice. J Neurovirol 24:398-410
Hu, Guoku; Liao, Ke; Niu, Fang et al. (2018) Astrocyte EV-Induced lincRNA-Cox2 Regulates Microglial Phagocytosis: Implications for Morphine-Mediated Neurodegeneration. Mol Ther Nucleic Acids 13:450-463
Schutt, Charles R; Gendelman, Howard E; Mosley, R Lee (2018) Tolerogenic bone marrow-derived dendritic cells induce neuroprotective regulatory T cells in a model of Parkinson's disease. Mol Neurodegener 13:26
Sillman, Brady; Bade, Aditya N; Dash, Prasanta K et al. (2018) Creation of a long-acting nanoformulated dolutegravir. Nat Commun 9:443
Domingo-Almenara, Xavier; Montenegro-Burke, J Rafael; Benton, H Paul et al. (2018) Annotation: A Computational Solution for Streamlining Metabolomics Analysis. Anal Chem 90:480-489
Thomas, Midhun B; Gnanadhas, Divya Prakash; Dash, Prasanta K et al. (2018) Modulating cellular autophagy for controlled antiretroviral drug release. Nanomedicine (Lond) 13:2139-2154
Spooner, Rachel K; Wiesman, Alex I; Mills, Mackenzie S et al. (2018) Aberrant oscillatory dynamics during somatosensory processing in HIV-infected adults. Neuroimage Clin 20:85-91
Kiyota, Tomomi; Machhi, Jatin; Lu, Yaman et al. (2018) URMC-099 facilitates amyloid-? clearance in a murine model of Alzheimer's disease. J Neuroinflammation 15:137
Guijas, Carlos; Montenegro-Burke, J Rafael; Warth, Benedikt et al. (2018) Metabolomics activity screening for identifying metabolites that modulate phenotype. Nat Biotechnol 36:316-320
Kevadiya, Bhavesh D; Woldstad, Christopher; Ottemann, Brendan M et al. (2018) Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution. Theranostics 8:256-276

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