TY - JOUR
T1 - Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage
AU - Hu, Shuxian
AU - Sheng, Wen S.
AU - Lokensgard, James R.
AU - Peterson, Phillip K.
AU - Rock, R. Bryan
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/12/12
Y1 - 2009/12/12
N2 - The dopamine (DA)-rich midbrain is known to be a key target of human immunodeficiency virus (HIV)-1. Studies of simian immunodeficiency virus (SIV)-induced neuropathogenesis recently established that there is a major disruption within the nigrostriatal dopaminergic system characterized by marked depletion of dopaminergic neurons, microglial cell activation, and reactive astrocytes. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, experiments were performed to characterize the damage to dopaminergic neurons induced by HIV-1 gp120. Functional impairment was assessed by DA uptake, and neurotoxicity was measured by apoptosis and oxidative damage. Through the use of this mesencephalic neuronal/glial culture model, we were able to identify the relative sensitivity of dopaminergic neurons to gp120-induced damage, manifested as reduced function (decreased DA uptake), morphological changes, and reduced viability. We also showed that gp120-induced oxidative damage is involved in this neuropathogenic process.
AB - The dopamine (DA)-rich midbrain is known to be a key target of human immunodeficiency virus (HIV)-1. Studies of simian immunodeficiency virus (SIV)-induced neuropathogenesis recently established that there is a major disruption within the nigrostriatal dopaminergic system characterized by marked depletion of dopaminergic neurons, microglial cell activation, and reactive astrocytes. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, experiments were performed to characterize the damage to dopaminergic neurons induced by HIV-1 gp120. Functional impairment was assessed by DA uptake, and neurotoxicity was measured by apoptosis and oxidative damage. Through the use of this mesencephalic neuronal/glial culture model, we were able to identify the relative sensitivity of dopaminergic neurons to gp120-induced damage, manifested as reduced function (decreased DA uptake), morphological changes, and reduced viability. We also showed that gp120-induced oxidative damage is involved in this neuropathogenic process.
KW - Dopamine
KW - Gp120
KW - Neurons
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=77649132973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649132973&partnerID=8YFLogxK
U2 - 10.3109/13550280903296346
DO - 10.3109/13550280903296346
M3 - Article
C2 - 20175694
AN - SCOPUS:77649132973
VL - 15
SP - 401
EP - 410
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
SN - 1355-0284
IS - 5-6
ER -