HIV-tat protein mediation of neuroAIDS central nervous system pathology and behavioral deficits
Year: 2010
Type: dissertation
Abstract: This dissertation investigated the role of HIV-Tat protein in mediating behavioral dysfunction and neurodegeneration associated with NeuroAIDS. NeuroAIDS is the syndrome consisting of neuropsychological manifestations and central nervous system pathology resulting from HIV-1 infection. The syndrome is characterized by the progressive loss of cognitive and motor function, and is also linked to neuropsychological disturbances that include changes in mood, "personality", and drug abuse. Research suggests that the cognitive and neuropsychological dysfunction may have a common etiological and biological basis; it is theorized that the release of toxic viral proteins from HIV-infected cells is a key mechanism by which HIV-1 indirectly and adversely affects neurons. HIV-1 Tat viral protein has been implicated in the pathogenesis of HIV-1 neurological complications, but direct behavioral demonstrations are limited. The central hypothesis tested in this thesis is that HIV-Tat protein, when expressed in brain, mediates behavioral dysfunction and neurodegeneration in an exposure-dependent manner. Four studies tested this hypothesis using the GT-tg bigenic mouse. The GT-tg mouse possesses an inducible and brain-selective tat gene that codes for Tat protein. These mice were uniquely suited for this study, as the expression of Tat protein is under the control of the researcher through the administration of Doxycycline (Dox). The dosage and number of days mice are administered Dox may be varied in order to control the amount and the length of time of Tat expression.
DOI: 10.17760/d20000280
Author: Amanda Natalie Carey
Institution: Northeastern University
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2096564044