title: Methamphetamine toxicity and its implications during HIV-1 infection.
abstract: Over the past two decades methamphetamine (MA) abuse has seen a dramatic increase. The abuse of MA is particularly high in groups that are at higher risk for HIV-1 infection, especially men who have sex with men (MSM). This review is focused on MA toxicity in the CNS as well as in the periphery. In the CNS, MA toxicity is comprised of numerous effects, including, but not limited to, oxidative stress produced by dysregulation of the dopaminergic system, hyperthermia, apoptosis, and neuroinflammation. Multiple lines of evidence demonstrate that these effects exacerbate the neurodegenerative damage caused by CNS infection of HIV perhaps because both MA and HIV target the frontostriatal regions of the brain. MA has also been demonstrated to increase viral load in the CNS of SIV-infected macaques. Using transgenic animal models, as well as cultured cells, the HIV proteins Tat and gp120 have been demonstrated to have neurotoxic properties that are aggravated by MA. In addition, MA has been shown to exhibit detrimental effects on the blood-brain barrier (BBB) that have the potential to increase the probability of CNS infection by HIV. Although the effects of MA in the periphery have not been as extensively studied as have the effects on the CNS, recent reports demonstrate the potential effects of MA on HIV infection in the periphery including increased expression of HIV co-receptors and increased expression of inflammatory cytokines.
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA. Silversteinp@umkc.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Silverstein
authors.forename: Ankit
authors.initials: A
authors.lastname: Shah
authors.forename: Raeesa
authors.initials: R
authors.lastname: Gupte
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Piepho
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000821:virology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects* / Q000821:virology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D005334:Fever / Q000139:chemically induced / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D015699:HIV Envelope Protein gp120; D013287:Illicit Drugs; D054322:tat Gene Products, Human Immunodeficiency Virus; D008694:Methamphetamine; D004298:Dopamine