title: Cocaine and HIV-1 interplay in CNS: cellular and molecular mechanisms.
abstract: Although antiretrovirals are the mainstay of therapy against HIV infection, neurological complications associated with the virus continue to hamper quality of life of the infected individuals. Drugs of abuse in the infected individuals further fuel the epidemic. Epidemiological studies have demonstrated that abuse of cocaine resulted in acceleration of HIV infection and the progression of NeuroAIDS. Cocaine has not only been shown to play a crucial role in promoting virus replication, but also has diverse but often deleterious effects on various cell types of the CNS. In the neuronal system, cocaine exposure results in neuronal toxicity and also potentiates gp120-induced neurotoxicity. In the astroglia and microglia, cocaine exposure leads to up-regulation of pro-inflammatory mediators such as cytokines and chemokines. These in turn, can lead to neuroinflammation and transmission of toxic responses to the neurons. Additionally, cocaine exposure can also lead to leakiness of the blood-brain barrier that manifests as enhanced transmigraiton of leukocytes/monocytes into the CNS. Both in vitro and in vivo studies have provided valuable tools in exploring the role of cocaine in mediating HIV-associated neuropathogenesis. This review summarizes previous studies on the mechanism(s) underlying the interplay of cocaine and HIV as it relates to the CNS.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. sbuch@unmc.edu
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
authors.forename: Minglei
authors.initials: M
authors.lastname: Guo
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.forename: Blaise
authors.initials: B
authors.lastname: Mathias-Costa
authors.forename: Vijeta
authors.initials: V
authors.lastname: Singh
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Tsung-Ping
authors.initials: TP
authors.lastname: Su
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000503:physiopathology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000378:metabolism*; D003042:Cocaine / Q000009:adverse effects / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D018450:Disease Progression; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D015699:HIV Envelope Protein gp120; D018836:Inflammation Mediators; D003042:Cocaine