Mark W Burke
Howard University, USA
Scientific Tracks Abstracts: Neurochem Neuropharm
Pediatric HIV infection remains a global health crisis with an estimated 650 children under the age of 15 years becoming infected with HIV-1 each day. Only about 25% of the estimated 2.5 million children under the age of 14 living with HIV-1 receive anti-retroviral therapy (ART). Perinatally HIV-1 infected individuals are disproportionately affected by HIV-1 related neurological impairments in comparison to adult infected patients and will often display neurobehavioral deficits prior to significant immunosuppression. Neurocognitive impairment is associated with a greater risk for disease progression and poorer morbidity, even in the advent of ART. As evidenced from the scarcity of neuroimaging and pathological reports, a main and obvious obstacle in pediatric HIV-1 research is sample access, therefore, it is critical to design and test potential intervention therapies in pediatric animal model systems. To this end, the present project takes advantage of ongoing pediatric SIV pathogenesis and vaccine studies to test the hypotheses associated with the neurological consequences of pediatric SIV infection. Perinatal rhesus macaques (Macaca mulatta) received intravenous inoculation with 100 tissue culture infectious doses 50% (TCID50) of SIVmac251 or vehicle (control n=4). Plasma viral loads were quantified by real-time RT-PCR. After a 6-18 week survival time, the animals were sacrificed and the brains prepared for quantitative histopathological analysis. Serialsections spanning the entire hippocampus were immunostained for SOX-2, glial fibrillary acidic protein (GFAP), nestin, or doublecortin that are putative markers for actively proliferating stem cells, astrocytes and immature neurons respectively. Data from this model indicates that, within two months of infection, SIV significantly reduces the hippocampal neuronal population in the pyramidal layer of the CA1, CA2, and CA3 sub-regions. There is also a loss of nestin- and doublcortin-positive neurons indicating a reduction in immature neurons along with a reduction in SOX-2 positive cells. The loss of neurogenic capacity may contribute to the rapid and persistent neurocognitive decline associated with pediatric HIV infection. This model presents a platform in which to test therapeutic interventions aimed at ameliorating the negative consequences of HIV-1 in the CNS, specifically targeting the neurogenesis pathway.
Mark W Burke received his Bachelor of Arts (Psychology) from SUNY Plattsburgh in upstate New York in 1996. He then went on to complete his Doctorate at McGill University in Montreal (Biology) and a Post-doctoral fellowship in Physiology at the Université de Montréal. In 2010, he joined the Department of Physiology at Howard University as an Assistant Professor. His research focuses on neurodevelopment and the effects of developmental intrusions in non-human primates.
Email: mark.burke@Howard.edu
