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Standardization and Optimization of the Detection of Neurogranin (Nrgn), a Synaptic Protein, using the 3D CNS Organoid Model of Human Immunodeficiency Virus (HIV-1) Infection

Carper, Abigail (2023) Standardization and Optimization of the Detection of Neurogranin (Nrgn), a Synaptic Protein, using the 3D CNS Organoid Model of Human Immunodeficiency Virus (HIV-1) Infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Human Immunodeficiency virus 1 (HIV-1) enters the central nervous system (CNS) and establishes infection during early stages of infection within the brain. Despite advancements in treatment with combination of antiviral therapies (ART), this chronic infection results in HIV-1 associated neurological disorders (HAND) in more than 60% of infected individuals, characterized by memory impairments and executive function deficits in people with HIV-1 (PWH). Although ART successfully controls systemic viral load, low level viral replication still occurs in the brain, creating chronic neuroinflammation due to release of viral protein and other neurotoxic factors which then leads to neuronal damage. Understanding how HIV-1 damages neurons in the brain is needed to develop treatment options and to improve the quality of life in PWH. Neurogranin (Nrgn) is a postsynaptic protein found in the dendritic spines of neurons and plays an important role in synaptic plasticity, memory, and learning. Nrgn has previously been shown to be dysregulated by HIV-1 infection, but the mechanism is less understood. To further understand Nrgn dysregulation within the CNS, our laboratory has recently developed an in vitro 3D CNS organoid model. My project aims to standardize and optimize the immunofluorescent staining protocol for the detection of Nrgn along with the identification of multiple cell types found within the 3D HIV-1 CNS organoid in 2D cell culture, human brain tissue samples and ultimately 3D organoid tissue samples.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Carper, Abigailalc359@pitt.eualc359
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduvelpandi
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
Committee MemberRodriguez-Bey, Guillmerogrb50@pitt.edugrb50
Date: 24 August 2023
Date Type: Publication
Defense Date: 8 August 2023
Approval Date: 24 August 2023
Submission Date: 11 August 2023
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 56
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: HIV-1, Neurogranin, CNS organoid
Date Deposited: 24 Aug 2023 18:01
Last Modified: 24 Aug 2023 18:01
URI: http://d-scholarship.pitt.edu/id/eprint/45326

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