Pilot Award Recipient: Mark Burke, PhD

Altered Neurodevelopment in Pediatric HIV Infection

September 15, 2012

Pediatric HIV infection remains a global health crisis with a worldwide infection rate of 2.5 million (WHO, Geneva Switzerland, 2009). Children are much more susceptible to HIV-1 neurological impairments than adults, which is exacerbated by co-infections. A main and obvious obstacle in pediatric HIV research is sample access. The proposed studies will take advantage of ongoing pediatric SIV pathogenesis and vaccine studies in Dr. Abel's lab to maximize the use of nonhuman primate resources by expanding on the original pediatric SIV-related immunology studies to include quantitative neuropathology studies. We hypothesize that neonatal SIV-infection will induce neuroinflammation resulting in neuronal death and impaired neurogenesis. Newborn rhesus macaques (Macacca mulatta) that received oral inoculation with a repeated-exposure of SIVmac251 (n-11) or vehicle (control n=6) will be used to test this hypothesis. After a 6-18 week survival time, the animals were sacrificed and the brains sent to Howard University for quantitative histopathological analysis. AIM 1 will test the hypothesis that neonatal SIV infection will result in a neuroinflammatory reaction as revealed through alterations in neuroglia (astrocytes and microglia) and expression of endocannabinoid receptors in the hippocampus and frontal cortex. In AIM 2 we will determine the extent of pediatric SIV-induced neurodegeneration as revealed through alterations in neuronal populations and neurogenesis in the hippocampus and frontal cortex. The goal of this project is to assess the impact of early HIV infection on the brain towards the long-term goal of evaluating treatment paradigms designed to protect the integrity of the developing brain from combined viral and bacterial infections through an interdisciplinary approach.