ASEMV 2017—Morphine-Mediated Potentiation of HIV-Associated Neurological Disorder (HAND)

On Monday morning, October 9, Shilpu Buch, PhD, Professor and Vice-Chair for Research, Director of the Nebraska Center for Substance Abuse Research, Nebraska Medical Center, University of Nebraska, presented on “Exosomal miRNA-Mediated Loss of Pericyte Coverage at the Blood-Brain Barrier: Implications for Morphine-Mediated Potentiation of HIV-Associated Neurological Disorder (HAND).” Dr. Buch began by noting that both in vitro and in vivo studies have shown that morphine potentiates the neurodegenerative effecs of HIV on the central nervous system (CNS). BBB breach by toxic stimuli is associated with the transmigration of monocytes and leukocyts into the brain, she said. Dr. Buch reported that three cell types are key to the blood-brain barrier (BBB). These are endothelial cells, astrocytes, and pericytes. She said that astrocyte-pericyte cross-talk is critical to BBB integrity. She said that pericytes regulate the BBB and that morphine reduces pericyte coverage of the BBB, resulting in cognitive impairment ant neuroinflammation. The underlying mechanism(s) by which morphine-exposed astrocytes regulate pericytes at the BBB, remains unknown. Previously, her group had identified a wide array of microRNAs (miRs) that are dysregulated in the CNS of SIV-infected, morphine-dependent macaques. In addition, her group has shown in vitro thatEVs released from morphine- and HIV-protein-Tat-exposed astrocytes can shuttle miRNAs, which, in turn, are taken up by neurons, leading to neuronal dysfunction.
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