Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Interactions of opioid and chemokine receptor systems: implications in HIV neuropathogenesis
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2006
DOI:
https://doi.org/10.17918/00003602
Abstract
A substantial proportion of the HIV-1 infected individuals are intravenous drug users, many of which abuse opiates (Donahoe and Vlahov, 1998). It has been postulated that opiate abuse promotes HIV-1 infection and disease progression, and that opioids can modulate the immune system (Donahoe and Vlahov, 1998; Peterson et al., 1998). Human immunodeficiency virus-1 (HIV-1) can induce a syndrome of cognitive and motor dysfunction that affects about 30% of untreated patients and about 10% of patients treated with antiretrovirals (Dore et al., 1999; Major et al., 2000; Sacktor et al., 2001; Sacktor et al., 2002). This syndrome has been designated HIV-1 associated dementia (HAD) and is due to neuronal loss and dysfunction in various regions of the brain (Price et al., 1988; Masliah et al., 1992). One mechanism of HIV-1 induced cell death and dysfunction is thought to occur via the HIV viral protein gp120. The gp120-mediated cell death occurs through chemokine receptors present on both neuronal and glial cells. The gp120 neurotoxicity appears to be caused by apoptotic signaling cascades initiated by binding of gp120 to chemokine receptors expressed on the surface of neurons and glia (Meucci et al., 1998; Kaul and Lipton, 1999; Meucci et al., 2000). Recent data from various labs have shown a direct interaction of opioids and their receptors with the HIV co-receptors CXCR4 and CCR5 on immune cells (Hu et al., 2000; Mahajan et al., 2002; Steele et al., 2003; Szabo et al., 2003). Furthermore, epidemiology studies indicate that opiates may enhance HIV neuropathology. This proposal sets out to explore the interactions between the [mu]-opioid and CXCR4 chemokine receptor systems in neuronal cells, both at the receptor level and the subsequent signaling pathways associated with each in the context of HIV associated dementia. Our hypothesis is that [mu]-opioid agonists modulate CXCR4 chemokine receptor activation and thus may alter the chemokine-induced cell signaling events, which play a role in neuronal survival. The data will provide insight into the interaction of the two distinct receptor systems and allow for a better understanding of the increased progression of HAD in opioid users.
Metrics
6 File views/ downloads
14 Record Views
Details
- Title
- Interactions of opioid and chemokine receptor systems
- Creators
- Jeegar P. Patel
- Contributors
- Olimpia Meucci (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xvi, 241 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991021889053304721