TY - JOUR
T1 - Cocaine
T2 - A catalyst for human immunodeficiency virus-associated dementia
AU - Dhillon, Navneet K.
AU - Gadgil, Milind
AU - Rahardja, Andy
AU - Callen, Shannon
AU - Sidelnik, Alex
AU - Renfrow, Duncan
AU - Moradi, Amanda
AU - Dhillon, Sukhbir
AU - Kenjale, Himanshu
AU - Kumar, Anil
AU - Buch, Shilpa J.
PY - 2008
Y1 - 2008
N2 - Injection drug use has been recognized as a major risk factor for AIDS from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States can both impair the functions of macrophages & CD4+ lymphocytes and also activate HIV-1 expression in these cells. Cocaine is a multifactorial agent that acts globally to impair the functioning of brain resident cells through multiple pathways. The drug not only promotes virus replication in macrophages, microglia and astrocytes, but can also upregulate CCR5 coreceptor, and reciprocally inhibit its ligands, thereby increasing virus infectivity. Cocaine is known to modulate astroglial function and activation. Cocaine causes a myriad of toxic responses in the neurons: a) it synergizes with viral proteins, Tat and gp120 resulting in exacerbated neuronal apoptosis, b) it causes calcium mobilization and, c) generation of reactive oxygen species. Additionally, cocaine also exerts potent effects on microvascular permeability, thereby impacting the influx of virus-infected inflammatory cells in brain parenchyma. By amplifying the various arms of the toxic responses that characterize HIV-associated dementia (HAD), cocaine skews the balance in favor of the virus leading to accelerated progression and severity of dementia.
AB - Injection drug use has been recognized as a major risk factor for AIDS from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States can both impair the functions of macrophages & CD4+ lymphocytes and also activate HIV-1 expression in these cells. Cocaine is a multifactorial agent that acts globally to impair the functioning of brain resident cells through multiple pathways. The drug not only promotes virus replication in macrophages, microglia and astrocytes, but can also upregulate CCR5 coreceptor, and reciprocally inhibit its ligands, thereby increasing virus infectivity. Cocaine is known to modulate astroglial function and activation. Cocaine causes a myriad of toxic responses in the neurons: a) it synergizes with viral proteins, Tat and gp120 resulting in exacerbated neuronal apoptosis, b) it causes calcium mobilization and, c) generation of reactive oxygen species. Additionally, cocaine also exerts potent effects on microvascular permeability, thereby impacting the influx of virus-infected inflammatory cells in brain parenchyma. By amplifying the various arms of the toxic responses that characterize HIV-associated dementia (HAD), cocaine skews the balance in favor of the virus leading to accelerated progression and severity of dementia.
KW - Blood brain barrier
KW - Cocaine
KW - HIV
KW - Transcription factors
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U2 - 10.3844/ajidsp.2008.131.139
DO - 10.3844/ajidsp.2008.131.139
M3 - Article
AN - SCOPUS:41149126601
SN - 1553-6203
VL - 4
SP - 131
EP - 139
JO - American Journal of Infectious Diseases
JF - American Journal of Infectious Diseases
IS - 2
ER -