PMID- 16967504
OWN - NLM
STAT- MEDLINE
DCOM- 20061211
LR  - 20131121
IS  - 0022-3034 (Print)
IS  - 0022-3034 (Linking)
VI  - 66
IP  - 12
DP  - 2006 Oct
TI  - Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120 
      reduces glial cell-line derived neurotrophic factor levels and causes apoptosis 
      in the substantia nigra.
PG  - 1311-21
AB  - Uninfected neurons of the substantia nigra (SN) degenerate in human 
      immunodeficiency virus (HIV)-positive patients through an unknown etiology. The 
      HIV envelope glycoprotein 120 (gp120) causes apoptotic neuronal cell death in the 
      rodent striatum, but its primary neurotoxic mechanism is still under 
      investigation. Previous studies have shown that gp120 causes neurotoxicity in the 
      rat striatum by reducing brain-derived neurotrophic factor (BDNF). Because glial 
      cell line-derived neurotrophic factor (GDNF) and BDNF are neurotrophic factors 
      crucial for the survival of dopaminergic neurons of the SN, we investigated 
      whether gp120 reduces GDNF and BDNF levels concomitantly to induce apoptosis. 
      Rats received a microinjection of gp120 or vehicle into the striatum and were 
      sacrificed at various time intervals. GDNF but not BDNF immunoreactivity was 
      decreased in the SN by 4 days in gp120-treated rats. In these animals, a 
      significant increase in the number of caspase-3- positive neurons, both tyrosine 
      hydroxylase (TH)-positive and -negative, was observed. Analysis of TH 
      immunoreactivity revealed fewer TH-positive neurons and fibers in a medial and 
      lateral portion of cell group A9 of the SN, an area that projects to the 
      striatum, suggesting that gp120 induces retrograde degeneration of nigrostriatal 
      neurons. We propose that dysfunction of the nigrostriatal dopaminergic system 
      associated with HIV may be caused by a reduction of neurotrophic factor 
      expression by gp120.
CI  - (c) 2006 Wiley Periodicals, Inc.
FAU - Nosheny, Rachel L
AU  - Nosheny RL
AD  - Department of Neuroscience, Georgetown University Medical Center, Washington DC 
      20057, USA.
FAU - Bachis, Alessia
AU  - Bachis A
FAU - Aden, Sadia A
AU  - Aden SA
FAU - De Bernardi, Maria A
AU  - De Bernardi MA
FAU - Mocchetti, Italo
AU  - Mocchetti I
LA  - eng
GR  - NS 040670/NS/NINDS NIH HHS/United States
GR  - NS046234/NS/NINDS NIH HHS/United States
GR  - NS047977/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurobiol
JT  - Journal of neurobiology
JID - 0213640
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (HIV Envelope Protein gp120)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - AIDS Dementia Complex/metabolism/physiopathology
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Axonal Transport/physiology
MH  - Basal Ganglia Diseases/metabolism/physiopathology/virology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Caspase 3/metabolism
MH  - Corpus Striatum/metabolism/physiopathology/virology
MH  - Disease Models, Animal
MH  - Dopamine/metabolism
MH  - Down-Regulation/physiology
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - HIV Envelope Protein gp120/*metabolism/toxicity
MH  - HIV-1
MH  - Male
MH  - Nerve Degeneration/metabolism/*physiopathology/virology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substantia Nigra/metabolism/*physiopathology/virology
MH  - Tyrosine 3-Monooxygenase/metabolism
EDAT- 2006/09/13 09:00
MHDA- 2006/12/12 09:00
CRDT- 2006/09/13 09:00
PHST- 2006/09/13 09:00 [pubmed]
PHST- 2006/12/12 09:00 [medline]
PHST- 2006/09/13 09:00 [entrez]
AID - 10.1002/neu.20288 [doi]
PST - ppublish
SO  - J Neurobiol. 2006 Oct;66(12):1311-21. doi: 10.1002/neu.20288.