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1. Putatunda, Raj. HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION.
Degree: PhD, 2018, Temple University
While antiretroviral therapy (ART) regimens have significantly decreased the mortality rate in patients with HIV-1 infection and subsequent opportunistic infections, the co-morbidities continue to rise. Some of these co-morbidities include cardiomyopathies, metabolic dysfunction, accelerated aging, and most notably, neurocognitive deficits. HIV-1 associated neurocognitive disorders (HAND) denote a spectrum of neurocognitive deficits that are either asymptomatic in nature (asymptomatic neurocognitive impairments, ANI), mild to moderate in intensity (mild neurocognitive disorders, MND), or robust in nature (HIV-associated dementia, HAD). Thanks to the development of ART regimens, the incidence of HAD dramatically decreased. However, the emergence of ANI and MND continues to increase in the HIV-1 patient population. While the multifaceted nature behind the central nervous system (CNS) neuropathology of HIV-1 infection is not completely understood, dysregulated blood-brain barrier (BBB) integrity and the “Trojan-Horse” type mechanism of HIV-1 infection have been proposed as the cellular mechanisms underlying HAND. HIV-1 infects CD4+ T-lymphocytes and monocytes in the peripheral circulatory system. After these infected cells cross the BBB into the CNS, they release toxic viral proteins and viral particles onto microglia and astrocytes. These glial cells become activated, and release a plethora of inflammatory cytokines that further damage neurons via dysregulated neurotransmitter homeostasis, synaptodendritic damage, and calcium-mediated apoptotic pathways. At the same time, the virus may establish a state of latency in these microglia, perivascular macrophages, and astrocytes, which would allow for the long-term persistence of HIV-1 in the CNS. Recently, several studies have demonstrated that neural stem cells (NSCs) are capable of being productively and latently infected with HIV-1. This may be due to the fact that the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and the circumventricular organs are highly vascularized, allowing potential direct contact of HIV-1 with NSCs. Additionally, the “Trojan” T-cells and macrophages could possibly release viral particles directly onto NSCs, and also transmit the virus through the formation of immunological synapses with NSCs. Therefore, the central hypothesis in this dissertation is that NSCs may serve as a novel CNS reservoir through which HIV-1 infection persists, and subsequently lead to neurocognitive impairments through dysregulating adult neurogenesis. Adult neurogenesis is a dynamic process that describes the generation of new neurons and glial cells from NSCs and neural progenitor cells (NPCs). This process mainly takes place in two areas of the brain: the SVZ around the lateral ventricles, and the SGZ within the dentate gyrus of the hippocampus. New neurons generated in these two neurogenic niches integrate into their respective circuitries to modulate olfactory stimuli and aid in memory acquisition/consolidation processes.…Advisors/Committee Members: Hu, Wenhui;, Qin, Xuebin, Barbe, Mary F., Kim, Seonhee, Ramirez, Servio, Bethea, John R.;.
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APA (6th Edition):
Putatunda, R. (2018). HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,514815
Chicago Manual of Style (16th Edition):
Putatunda, Raj. “HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION.” 2018. Doctoral Dissertation, Temple University. Accessed October 26, 2020. http://digital.library.temple.edu/u?/p245801coll10,514815.
MLA Handbook (7th Edition):
Putatunda, Raj. “HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION.” 2018. Web. 26 Oct 2020.
Putatunda R. HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION. [Internet] [Doctoral dissertation]. Temple University; 2018. [cited 2020 Oct 26]. Available from: http://digital.library.temple.edu/u?/p245801coll10,514815.
Council of Science Editors:
Putatunda R. HIV-1 INFECTION OF NEURAL STEM CELLS RESULTS IN COGNITIVE DEFICITS THROUGH ADULT NEUROGENIC MODULATION. [Doctoral Dissertation]. Temple University; 2018. Available from: http://digital.library.temple.edu/u?/p245801coll10,514815