PMID- 19457078
OWN - NLM
STAT- MEDLINE
DCOM- 20090731
LR  - 20131121
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 110
IP  - 2
DP  - 2009 Jul
TI  - Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from 
      inflammatory degeneration via BDNF-mediated signaling.
PG  - 707-18
LID - 10.1111/j.1471-4159.2009.06171.x [doi]
AB  - Functions of retinoic acid receptors (RARs) in adult CNS have been poorly 
      characterized. Here we investigated potential neuroprotective action of 
      tamibarotene (Am80), an RARalpha/beta agonist available for the treatment of 
      acute promyelocytic leukemia, on midbrain dopaminergic neurons. Am80 protected 
      dopaminergic neurons in rat midbrain slice culture from injury mediated by 
      lipopolysaccharide-activated microglia, without affecting production of nitric 
      oxide, a key mediator of cell injury. The effect of Am80 was mimicked by another 
      RAR agonist, TAC-101, but not by a retinoid X receptor agonist, HX630, and HX630 
      did not synergize with Am80. We observed neuronal expression of RARalpha and 
      RARbeta in midbrain slice culture and also found that Am80 increased tissue level 
      of brain-derived neurotrophic factor (BDNF) mRNA. Exogenous BDNF prevented 
      dopaminergic neurodegeneration, and the neuroprotective effect of Am80 was 
      suppressed by a TrkB inhibitor, K252a, or by anti-BDNF neutralizing antibody. 
      These results reveal a novel action of RARs mediated by enhancement of BDNF 
      expression. Finally, oral administration of Am80 prevented dopaminergic cell loss 
      in the substantia nigra induced by local injection of lipopolysaccharide in mice, 
      indicating that RARs are a promising target of therapeutics for neurodegenerative 
      disorders.
FAU - Katsuki, Hiroshi
AU  - Katsuki H
AD  - Department of Chemico-Pharmacological Sciences, Kumamoto University, Japan. 
      hkatsuki@gpo.kumamoto-u.ac.jp
FAU - Kurimoto, Emi
AU  - Kurimoto E
FAU - Takemori, Sachiko
AU  - Takemori S
FAU - Kurauchi, Yuki
AU  - Kurauchi Y
FAU - Hisatsune, Akinori
AU  - Hisatsune A
FAU - Isohama, Yoichiro
AU  - Isohama Y
FAU - Izumi, Yasuhiko
AU  - Izumi Y
FAU - Kume, Toshiaki
AU  - Kume T
FAU - Shudo, Koichi
AU  - Shudo K
FAU - Akaike, Akinori
AU  - Akaike A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090515
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Benzoates)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 08V52GZ3H9 (tamibarotene)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Benzoates/chemical synthesis/pharmacology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Dopamine/*physiology
MH  - Humans
MH  - Inflammation Mediators/metabolism/*physiology
MH  - Male
MH  - Mesencephalon/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Degeneration/metabolism/*prevention & control
MH  - Neurons/drug effects/*metabolism
MH  - Organ Culture Techniques
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Retinoic Acid/agonists/*metabolism/physiology
MH  - Retinoids/agonists/chemical synthesis/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Tetrahydronaphthalenes/chemical synthesis/pharmacology
EDAT- 2009/05/22 09:00
MHDA- 2009/08/01 09:00
CRDT- 2009/05/22 09:00
PHST- 2009/05/22 09:00 [entrez]
PHST- 2009/05/22 09:00 [pubmed]
PHST- 2009/08/01 09:00 [medline]
AID - JNC6171 [pii]
AID - 10.1111/j.1471-4159.2009.06171.x [doi]
PST - ppublish
SO  - J Neurochem. 2009 Jul;110(2):707-18. doi: 10.1111/j.1471-4159.2009.06171.x. Epub 
      2009 May 15.