title: Permeability of the blood-brain barrier to HIV-1 Tat.
abstract: Infection with human immunodeficiency virus-1 (HIV-1) is associated with dysfunctions of the central nervous system (CNS). HIV-1 induces its effects on the CNS by a variety of mechanisms, including by shedding the neurotoxic viral proteins such as gp120 and Tat. Both HIV-1 and gp120 have been shown to cross the blood-brain barrier (BBB). It is has not been determined, however, whether blood-borne Tat can cross the BBB. Here, we found that Tat crosses the BBB by a nonsaturable mechanism with a unidirectional influx rate of about 0.490 microl/g/min. About 0.126% of an intravenous dose of Tat enters each g of brain. Radioactively labeled albumin injected simultaneously did not cross the BBB. The hypothalamus, occipital cortex, and hippocampus were the regions of the brain most permeable to Tat. Nonsaturable brain-to-blood efflux also occurred, most likely with reabsorption into the blood of the cerebrospinal fluid. In conclusion, we found that Tat crossed the BBB bidirectionally. Such permeability could provide a mechanism by which Tat produced on one side of the BBB could affect neural or immune function on the other side.
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, GRECC, Veterans Affairs Medical Center-St. Louis and Saint Louis University School of Medicine, 915 N. Grand Boulevard, St. Louis, MO 63106, USA. bankswa@slu.edu
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Robinson
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology*; D015696:Gene Products, tat / Q000008:administration & dosage / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus