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Thesis
Effects of cocaine and HIV infection interaction on PSA expression in male and female mice
Master of Science (M.S.), Drexel University
Aug 2020
DOI:
https://doi.org/10.17918/00001394
Abstract
Substance use is highly common in human immunodeficiency virus (HIV) infected population. Both cocaine and HIV affect the cognition, partially via regulating the neuronal plasticity of the corticoaccumbens circuitry. Polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM) is highly expressed on cells in this circuitry and manipulates the synaptic plasticity and associated cognitive function. It has been demonstrated that ovarian hormones regulate synaptic plasticity and, further, alter cocaine-seeking behavior in females. Therefore, we hypothesize that the PSA expression might be changed across the estrous cycle in this circuitry in females. Moreover, HIV infection and cocaine may interact to impact cognition by altering the PSA levels in this circuitry in males and females. Immunohistochemistry on tissue from mice euthanized at different phases of the estrous cycle revealed that PSA expression was regulated in a region and phase dependent manner. We observed lower PSA immunoactivity in the prelimbic cortex (PrL) in the proestrus phase than in the estrus and diestrus phase in wild-type female mice. However, no alterations of PSA immunoactivity were found in the infralimbic cortex (IL), the nucleus accumbens shell (NAcS), and the nucleus accumbens core (NAcC). To assess the effects of HIV and cocaine, human-CD34+ male and female mice that allowed the HIV infection in the brain of mice underwent HIV inoculation and cocaine conditioned-place preference (CPP). We found that neither cocaine injection nor HIV inoculation altered the PSA immunoactivity. However, HIV mice showed higher cocaine CPP. Their preference scores were negatively correlated with PSA immunoactivity in the PrL and the NAcC. Overall, our studies suggested that HIV-exacerbated cocaine sensitivity may be associated with reductions in PSA in the corticoaccumbens circuitry. This may further be modulated by sex and estrous cycle.
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Details
- Title
- Effects of cocaine and HIV infection interaction on PSA expression in male and female mice
- Creators
- Fangyi Huang
- Contributors
- Peter J. Gaskill (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 54 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991014695135204721