PMID- 17445226
OWN - NLM
STAT- MEDLINE
DCOM- 20070712
LR  - 20220311
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 25
IP  - 8
DP  - 2007 Apr
TI  - Brain-derived neurotrophic factor prevents the nigrostriatal degeneration induced 
      by human immunodeficiency virus-1 glycoprotein 120 in vivo.
PG  - 2275-84
AB  - Glycoprotein 120 (gp120) from the T-tropic strain of the human immunodeficiency 
      virus type 1 has been shown to cause neuronal apoptosis through activation of the 
      chemokine receptor CXCR4. Therefore, reducing CXCR4 expression may prevent 
      gp120-mediated apoptosis. Brain-derived neurotrophic factor (BDNF) is known to 
      reduce both gp120 neurotoxicity and CXCR4 expression in vitro. The scope of this 
      work is to establish whether BDNF is neuroprotective against gp120 in vivo and, 
      if so, whether this effect correlates with its ability to down-regulate CXCR4. 
      Serotype 2 adeno-associated viral vector encoding for BDNF (rAAV-BDNF) or control 
      vector was microinjected into the striata of adult rats. Two weeks later gp120 
      was injected into the same striatum, and apoptosis determined. Pretreatment with 
      rAAV-BDNF prior to gp120 microinjection prevented caspase-3 activation as well as 
      in situ terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling in 
      the striatum and substantia nigra. In addition, rAAV-BDNF reversed the loss of 
      tyrosine hydroxylase immunoreactivity induced by gp120 in both areas. CXCR4 
      expression was then determined by immunohistochemistry and RT-PCR, and found to 
      be decreased in striata of rAAV-BDNF-treated rats. Conversely, BDNF heterozygous 
      mice exhibited an increase in CXCR4 mRNA levels compared to wild-type 
      littermates. Our data suggest that down-regulation of CXCR4 expression may 
      contribute to the neuroprotective activity of BDNF against gp120 toxicity in the 
      basal ganglia.
FAU - Nosheny, Rachel L
AU  - Nosheny RL
AD  - Department of Neuroscience, Georgetown University, EP04, New Research Building, 
      3970 Reservoir Road, NW Washington, DC, USA.
FAU - Ahmed, Farid
AU  - Ahmed F
FAU - Yakovlev, Alexander
AU  - Yakovlev A
FAU - Meyer, Edwin M
AU  - Meyer EM
FAU - Ren, Ke
AU  - Ren K
FAU - Tessarollo, Lino
AU  - Tessarollo L
FAU - Mocchetti, Italo
AU  - Mocchetti I
LA  - eng
GR  - NS040670/NS/NINDS NIH HHS/United States
GR  - NS046234/NS/NINDS NIH HHS/United States
GR  - NS047977/NS/NINDS NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, CXCR4)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Corpus Striatum/*pathology
MH  - Dopamine/metabolism
MH  - HIV Envelope Protein gp120/genetics/*metabolism
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microinjections
MH  - Neurons/cytology/metabolism/pathology
MH  - Neuroprotective Agents/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - Substantia Nigra/*pathology
MH  - Transgenes
MH  - Tyrosine 3-Monooxygenase/metabolism
EDAT- 2007/04/21 09:00
MHDA- 2007/07/13 09:00
CRDT- 2007/04/21 09:00
PHST- 2007/04/21 09:00 [pubmed]
PHST- 2007/07/13 09:00 [medline]
PHST- 2007/04/21 09:00 [entrez]
AID - EJN5506 [pii]
AID - 10.1111/j.1460-9568.2007.05506.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2007 Apr;25(8):2275-84. doi: 10.1111/j.1460-9568.2007.05506.x.