Michal Toborek
University of Miami, USA
Title: Blood-brain barrier approach to HIV infection and methamphetamine toxicity
Biography
Biography: Michal Toborek
Abstract
The blood-brain barrier (BBB) is the most prominent barrier of the CNS and represents the essential interface between the CNS and the blood stream. The intact BBB is maintained by tight junction (TJ) proteins and is a paramount determinant of brain homeostasis. Disruption of the BBB is frequently observed during drug abuse and brain infections by various pathogens, including HIV. Our results indicate that occludin, one of the major TJ proteins, is decreased upon methamphetamine (METH) exposure and that diminished occludin levels not only lead to the loss of integrity of the BBB but also stimulate HIV replication. The central hypothesis of our research is that cerebrovascular alterations at the BBB level induced by METH have profound impact on establishing and outcome of the brain infection by HIV. This project develops in the following three major research areas: 1) impact of occluding levels on HIV replication in BBB pericytes, 2) impact of disruption of BBB on aberrant neurogenesis of neural progenitor cells resulting in the development of cognitive dysfunction, and 3) behavioral intervention based on exercise for protection against METH and HIV-induced BBB dysfunction and neurocognitive alterations. This research offers a unique perspective on the interactions between METH and HIV via targeting the BBB. However, our results are relevant to other neurodegenerative diseases that have significant cerebrovascular components.