Date of Award

2018

Document Type

Open Access Dissertation

Department

Psychology

Sub-Department

College of Arts and Sciences

First Advisor

Rosemarie M. Booze

Abstract

Human Immunodeficiency Virus (HIV-1) afflicts nearly 38 million individuals worldwide (Joseph et al., 2013; “WHO | HIV/AIDS,” 2016). Despite the reduction in disease mortality due to increased use of antiretroviral medication, HIV-1 associated neurocognitive disorder (HAND) affects approximately 50% of HIV infected individuals (Antinori et al., 2007; Castellon, Hinkin, Wood, & Yarema, 1998; Castelo, Sherman, Courtney, Melrose, & Stern, 2006; Cysique & Brew, 2009; Heaton et al., 2011, 2015). The brain itself is particularly sensitive to HIV-1 related viral proteins and viral infection (Masliah, DeTeresa, Mallory, & Hansen, 2000), thus, it is vital to empirically examine potentially effective therapeutics which may be capable of improving cognition in HIV-1 patients. In the contemporary literature, cognitive deficiencies encompassed by HAND include deficits in: attention/information processing, language, abstraction-executive function, complex perceptual motor skills, memory (short-term and working memory), learning and recall, simple motor skills and sensory perceptual abilities, as defined by the most recent HIV-1 nosology (Antinori et al., 2007).

Therapeutics capable of improving neurocognitive dysfunction in the HIV-1 brain has yet to be established; therefore, the current study examined a potential therapeutic theoretically capable of improving HAND related cognitive dysfunction: physical activity. Physical activity has been shown to be the strongest environmental factor capable of promoting the genesis of new neurons in the subgranular zone of the hippocampal dentate gyrus (Fuss et al., 2014; Ji et al., 2014; Klein et al., 2016; M.-H. Lee et al., 2013; Naylor et al., 2008; van Praag, Christie, Sejnowski, & Gage, 1999; van Praag, Kempermann, & Gage, 1999; van Praag et al., 2002; van Praag, Shubert, Zhao, & Gage, 2005; Vivar & van Praag, 2013). Furthermore, when examining the relationship between physical activity and HIV-1 associated cognitive decline, there appears to be an association between acute physical activity and cognitive function in human HIV-1+ patients (Dufour et al., 2013, 2018), evidence which suggests physical activity may be capable of preserving/promoting cognitive function in the HIV-1 brain. The current study determined whether promoting neurogenesis through physical activity can act as a neuroprotective/neurorestorative therapeutic agent capable of attenuating the progression of HIV-1 cognitive pathology. Upon completion of the current study, the role of chronic HIV-1 viral protein expression on dentate gyrus neurogenesis in the HIV-1 transgenic (Tg) rat brain was empirically established. The current results provide evidence that HIV-1 viral proteins do inhibit neurogenesis (as determined by doublecortin immunolableling), and that wheel running did not significantly increase neurogenesis. However, wheel running significantly increased dendritic spine length, volume and head diameter, as well as dendritic length. These results suggest that physical activity may be an effective therapeutic for improving HIV-1-dependent neurological synaptodendritic damage due to the expression of HIV-1 viral proteins.

Rights

© 2018, Michael N. Cranston

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