PMID- 11516824
OWN - NLM
STAT- MEDLINE
DCOM- 20011101
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 105
IP  - 3
DP  - 2001
TI  - Involvement of the brain-derived neurotrophic factor/TrkB pathway in 
      neuroprotecive effect of cyclosporin A in forebrain ischemia.
PG  - 571-8
AB  - Recent studies have shown that cyclosporin A, a specific antagonist of 
      calcineurin, a phosphatase, ameliorates neuronal cell death in the CA1 sector of 
      the hippocampus after forebrain ischemia in animal models. The mechanism of this 
      neuroprotective effect, however, has not yet been established. Brain-derived 
      neurotrophic factor (BDNF), a member of the neurotrophins, is one of the potent 
      survival and developmental factors whose expression is regulated by cyclic 
      AMP-response element-binding protein (CREB). Activation of CREB is dependent on 
      its phosphorylation at Ser(133), and calcineurin has been reported to 
      dephosphorylate CREB via protein phosphatase 1. Based on these observations, we 
      attempted to investigate how cyclosporin A treatment would affect the changes of 
      phosphorylated CREB (pCREB), BDNF and its receptor tyrosine kinase B (TrkB) after 
      forebrain ischemia in rats. Phosphorylation of CREB was kept augmented throughout 
      the time course examined in cyclosporin A-treated animals, while it ceased 
      without cyclosporin A. Reverse transcription-polymerase chain reaction revealed 
      prolonged maintenance of BDNF mRNA expression in the CA1 sector of cyclosporin 
      A-treated animals. The protein expression of BDNF and TrkB appeared to be 
      up-regulated in cyclosporin A-treated animals, whereas it was transiently 
      up-regulated but decreased to the marginal level of expression without 
      cyclosporin A.From these results we suggest that cyclosporin A induces pCREB by 
      an inhibition of calcineurin, resulting in the induction of BDNF. The mechanisms 
      by which cyclosporin A protects the CA1 region from neuronal cell death in 
      forebrain ischemia may involve the interaction of pCREB, BDNF and TrkB.
FAU - Miyata, K
AU  - Miyata K
AD  - Department of Anesthesiology, Tokyo Medical University, Japan. 
      kmiyata@ops.dti.ne.jp
FAU - Omori, N
AU  - Omori N
FAU - Uchino, H
AU  - Uchino H
FAU - Yamaguchi, T
AU  - Yamaguchi T
FAU - Isshiki, A
AU  - Isshiki A
FAU - Shibasaki, F
AU  - Shibasaki F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain Ischemia/*drug therapy/metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/*drug effects/genetics/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/drug effects/metabolism
MH  - Cyclosporine/*pharmacology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hippocampus/drug effects/pathology/physiopathology
MH  - Immunohistochemistry
MH  - Male
MH  - Nerve Degeneration/drug therapy/physiopathology/prevention & control
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/*drug effects/metabolism
MH  - Transcription, Genetic/drug effects/physiology
MH  - Up-Regulation/*drug effects/physiology
EDAT- 2001/08/23 10:00
MHDA- 2001/11/03 10:01
CRDT- 2001/08/23 10:00
PHST- 2001/08/23 10:00 [pubmed]
PHST- 2001/11/03 10:01 [medline]
PHST- 2001/08/23 10:00 [entrez]
AID - S0306-4522(01)00225-1 [pii]
AID - 10.1016/s0306-4522(01)00225-1 [doi]
PST - ppublish
SO  - Neuroscience. 2001;105(3):571-8. doi: 10.1016/s0306-4522(01)00225-1.