PMID- 18646205
OWN - NLM
STAT- MEDLINE
DCOM- 20090122
LR  - 20181201
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 86
IP  - 15
DP  - 2008 Nov 15
TI  - Pitx3-transfected astrocytes secrete brain-derived neurotrophic factor and glial 
      cell line-derived neurotrophic factor and protect dopamine neurons in 
      mesencephalon cultures.
PG  - 3393-400
LID - 10.1002/jnr.21774 [doi]
AB  - The transcription factor Pitx3 is crucial for the development and differentiation 
      of dopamine (DA) neurons. Our previous work has shown the Pitx3 can up-regulate 
      the expression of brain-derived neurotrophic factor (BDNF) and glial cell 
      line-derived neurotrophic factor (GDNF) in neuroblastoma cell line SH-SY5Y. 
      Primary astrocytes are the major nonneuronal cells and can be easily modified 
      genetically to deliver therapeutic molecules into the brain, so we investigated 
      whether Pitx3 can increase the expression and secretion of BDNF and GDNF in 
      primary astrocytes. We first transfected Pitx3 plasmid in purified rat astrocytes 
      and collected the conditioned medium (CM) from the Pitx3-transfected cultures, 
      and then we measured the BDNF and GDNF levels from the CM and tested the 
      protective effect of the CM against rotenone-induced DA neuron injury in ventral 
      mesencephalon (VM) cultures. We found that the BDNF and GDNF levels were 1.4-fold 
      and 1.5-fold higher in the CM from Pitx3-transfected astrocytes than empty 
      vectors-transfected controls. Incubation with the CM from Pitx3-transfected 
      astrocytes significantly attenuated the rotenone-induced DA neuron injury, and 
      such protection can be significantly blocked by preincubation with antibodies 
      against either BDNF or GDNF, whereas preincubation with purified BDNF or GDNF 
      replicated the neuroprotection against rotenone-induced injury in VM cultures. 
      These results demonstrate that Pitx3-transfection in astrocytes can up-regulate 
      BDNF and GDNF expression and produce protective benefit to DA neurons, which 
      might be a potential therapeutic alternative for Parkinson's disease.
FAU - Yang, Dehua
AU  - Yang D
AD  - Institute of Health Sciences, Shanghai Institutes for Biological Sciences, 
      Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, 
      Shanghai, People's Republic of China.
FAU - Peng, Changgeng
AU  - Peng C
FAU - Li, Xuping
AU  - Li X
FAU - Fan, Xiaolan
AU  - Fan X
FAU - Li, Liang
AU  - Li L
FAU - Ming, Ming
AU  - Ming M
FAU - Chen, Sheng
AU  - Chen S
FAU - Le, Weidong
AU  - Le W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Transcription Factors)
RN  - 0 (homeobox protein PITX3)
RN  - 03L9OT429T (Rotenone)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/chemistry/metabolism
MH  - Dopamine/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Genetic Therapy/*methods
MH  - Glial Cell Line-Derived Neurotrophic Factor/*biosynthesis
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Mesencephalon/cytology/metabolism
MH  - Nerve Degeneration/chemically induced/prevention & control
MH  - *Neurons/drug effects/metabolism
MH  - Neurotoxins/toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Rotenone/toxicity
MH  - Transcription Factors/*genetics/metabolism
MH  - Transfection
EDAT- 2008/07/23 09:00
MHDA- 2009/01/23 09:00
CRDT- 2008/07/23 09:00
PHST- 2008/07/23 09:00 [pubmed]
PHST- 2009/01/23 09:00 [medline]
PHST- 2008/07/23 09:00 [entrez]
AID - 10.1002/jnr.21774 [doi]
PST - ppublish
SO  - J Neurosci Res. 2008 Nov 15;86(15):3393-400. doi: 10.1002/jnr.21774.