Neuroimmune and Epigenetic Alterations from HIV and Opioid Exposure In the CNS
Abstract
Introduction and Objective. HIV remains a significant worldwide health issue as does its relationship with the opioid epidemic. Substance abuse increases risk for the spread of HIV infection and is associated with treatment non-compliance, more rapid disease progression, and greater mortality. The impact of opioids on the immune system has been widely understood to induce immunosuppression, but it has also been more recently explored in its capacity to stimulate immune activity. In recent years, epigenetic modifications have been implicated in the development of opioid addiction. The unique impact of opioid abuse on the severity, progression, and prognosis of HIV-associated neurocognitive disorders (HAND) and its lasting epigenetic implications are not fully understood. HAND persists despite successful ART, for which there are currently no treatments. The objective of the current study is to examine mechanisms regulating HIV and opioid induced CNS dysfunction through a neuroimmune and epigenetic lens. We hypothesize that opioid and HIV-associated genetic and epigenetic responses can be used as biomarkers for neuropathology and we further speculate that targeting these modifications can abate the neuropathological effects endured due to exposure to HIV and opioid abuse. Methods. We analyzed alterations in innate and adaptive immune responses and chromatin modification enzymes within postmortem brain tissue of HIV patients with a history of drug abuse from the National NeuroAIDs Tissue Consortium in addition to a mouse model of opioid use disorder using the highly sensitive and reliable Qiagen RT2 Profiler PCR array. We also observed tolerance and antinociceptive effects of opioid exposure by performing the hot plate test in a mouse model of opioid use. Results. We found that the pathogen recognition receptors in the innate immune response showcased themselves as a major player in mediating proinflammatory pathways related to the advancement of HAND. We also found that chromatin remodeling occurs in response to prolonged exposure to HIV and drug use and promotes inflammation. Conclusions-Implications. The accumulated data helps create a general picture of neuroimmune and epigenetic mechanisms involved in the advancement of HIV and opioid indcued neurological impairment which could prove promising in identifying novel targets for improved diagnosis and therapeutic interventions.
Abstract Category
19. Neurology
Secondary Abstract Category
13. Infectious Diseases
Keywords
HIV, opioids, epigenetics, CNS, inflammation, neuroimmune, neurological impairment
Presentation Type
Poster Presentation
Neuroimmune and Epigenetic Alterations from HIV and Opioid Exposure In the CNS
Introduction and Objective. HIV remains a significant worldwide health issue as does its relationship with the opioid epidemic. Substance abuse increases risk for the spread of HIV infection and is associated with treatment non-compliance, more rapid disease progression, and greater mortality. The impact of opioids on the immune system has been widely understood to induce immunosuppression, but it has also been more recently explored in its capacity to stimulate immune activity. In recent years, epigenetic modifications have been implicated in the development of opioid addiction. The unique impact of opioid abuse on the severity, progression, and prognosis of HIV-associated neurocognitive disorders (HAND) and its lasting epigenetic implications are not fully understood. HAND persists despite successful ART, for which there are currently no treatments. The objective of the current study is to examine mechanisms regulating HIV and opioid induced CNS dysfunction through a neuroimmune and epigenetic lens. We hypothesize that opioid and HIV-associated genetic and epigenetic responses can be used as biomarkers for neuropathology and we further speculate that targeting these modifications can abate the neuropathological effects endured due to exposure to HIV and opioid abuse. Methods. We analyzed alterations in innate and adaptive immune responses and chromatin modification enzymes within postmortem brain tissue of HIV patients with a history of drug abuse from the National NeuroAIDs Tissue Consortium in addition to a mouse model of opioid use disorder using the highly sensitive and reliable Qiagen RT2 Profiler PCR array. We also observed tolerance and antinociceptive effects of opioid exposure by performing the hot plate test in a mouse model of opioid use. Results. We found that the pathogen recognition receptors in the innate immune response showcased themselves as a major player in mediating proinflammatory pathways related to the advancement of HAND. We also found that chromatin remodeling occurs in response to prolonged exposure to HIV and drug use and promotes inflammation. Conclusions-Implications. The accumulated data helps create a general picture of neuroimmune and epigenetic mechanisms involved in the advancement of HIV and opioid indcued neurological impairment which could prove promising in identifying novel targets for improved diagnosis and therapeutic interventions.