PMID- 18588860
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20211020
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1227
DP  - 2008 Aug 28
TI  - Brain-derived neurotrophic factor modulates expression of chemokine receptors in 
      the brain.
PG  - 1-11
LID - 10.1016/j.brainres.2008.05.086 [doi]
AB  - Chemokine receptors, and in particular CXCR4 and CCR5 play a key role in the 
      neuropathogenesis of Human Immunodeficiency Virus-1 (HIV)4 associated dementia 
      (HAD). Thus, new insight into the expression of CXCR4 in the central nervous 
      system may help develop therapeutic compounds against HAD. Brain-derived 
      neurotrophic factor (BDNF) is neuroprotective in vitro against two strains of the 
      HIV envelope protein gp120 that binds to CXCR4 or CCR5. Therefore, we examined 
      whether BDNF modulates chemokine receptor expression in vivo. The content of 
      CXCR4 mRNA and proteins was determined in the cerebral cortex and hippocampus of 
      6-month-old BDNF heterozygous mice and wild type littermates by using polymerase 
      chain reaction and immunohistochemistry, respectively. BDNF heterozygous mice 
      exhibited an increase in CXCR4 mRNA compared to wild type. Histological analyses 
      revealed an up-regulation of CXCR4 immunoreactivity mainly in neurons. Most of 
      these neurons were positive for TrkB, the BDNF receptor with a tyrosine kinase 
      activity. Increases in CXCR4 mRNA levels were observed in 18-month-old BDNF 
      heterozygous mice but not in 7-day-old mice, suggesting that the modulatory role 
      of BDNF occurs only in mature animals. To determine whether BDNF affects also 
      CXCR4 internalization, SH-SY5Y neuroblastoma cells were exposed to BDNF and cell 
      surface CXCR4 levels were measured at various times. BDNF induced CXCR4 
      internalization within minutes. Lastly, BDNF heterozygous mice showed higher 
      levels of CCR5 and CXCR3 mRNA than wild type in the cerebral cortex, hippocampus 
      and striatum. Our data indicate that BDNF may modulate the availability of 
      chemokine receptors implicated in HIV infection.
FAU - Ahmed, Farid
AU  - Ahmed F
AD  - Department of Neuroscience, Georgetown University Medical Center, Washington DC, 
      USA.
FAU - Tessarollo, Lino
AU  - Tessarollo L
FAU - Thiele, Carol
AU  - Thiele C
FAU - Mocchetti, Italo
AU  - Mocchetti I
LA  - eng
GR  - R01 NS040670/NS/NINDS NIH HHS/United States
GR  - R01 NS040670-07/NS/NINDS NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - NS 040670/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20080613
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, CXCR3)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (Rpl19 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 5.2.1.- (Cyclophilins)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism/pharmacology
MH  - Cell Line, Tumor
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Corpus Striatum/drug effects/metabolism
MH  - Cyclophilins/genetics/metabolism
MH  - Fluorescent Antibody Technique, Direct
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Heterozygote
MH  - Hippocampus/drug effects/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/cytology/drug effects/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, trkB/genetics/metabolism
MH  - Receptors, CCR5/genetics/metabolism
MH  - Receptors, CXCR3/genetics/metabolism
MH  - Receptors, CXCR4/genetics/metabolism
MH  - Receptors, Chemokine/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Proteins/genetics/metabolism
PMC - PMC2601566
MID - NIHMS69267
EDAT- 2008/07/01 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/08/28
CRDT- 2008/07/01 09:00
PHST- 2007/10/22 00:00 [received]
PHST- 2008/05/14 00:00 [revised]
PHST- 2008/05/24 00:00 [accepted]
PHST- 2008/07/01 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/07/01 09:00 [entrez]
PHST- 2009/08/28 00:00 [pmc-release]
AID - S0006-8993(08)01305-X [pii]
AID - 10.1016/j.brainres.2008.05.086 [doi]
PST - ppublish
SO  - Brain Res. 2008 Aug 28;1227:1-11. doi: 10.1016/j.brainres.2008.05.086. Epub 2008 
      Jun 13.