PMID- 23844255
OWN - NLM
STAT- MEDLINE
DCOM- 20140207
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - delta-Opioid receptor activation rescues the functional TrkB receptor and protects 
      the brain from ischemia-reperfusion injury in the rat.
PG  - e69252
LID - 10.1371/journal.pone.0069252 [doi]
LID - e69252
AB  - OBJECTIVES: delta-opioid receptor (DOR) activation reduced brain ischemic infarction 
      and attenuated neurological deficits, while DOR inhibition aggravated the 
      ischemic damage. The underlying mechanisms are, however, not well understood yet. 
      In this work, we asked if DOR activation protects the brain against ischemic 
      injury through a brain-derived neurotrophic factor (BDNF) -TrkB pathway. METHODS: 
      We exposed adult male Sprague-Dawley rats to focal cerebral ischemia, which was 
      induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (60 nmol), 
      antagonist Naltrindole (100 nmol) or artificial cerebral spinal fluid was 
      injected into the lateral cerebroventricle 30 min before MCAO. Besides the 
      detection of ischemic injury, the expression of BDNF, full-length and truncated 
      TrkB, total CREB, p-CREB, p-ATF and CD11b was detected by Western blot and 
      fluorescence immunostaining. RESULTS: DOR activation with TAN-67 significantly 
      reduced the ischemic volume and largely reversed the decrease in full-length TrkB 
      protein expression in the ischemic cortex and striatum without any appreciable 
      change in cerebral blood flow, while the DOR antagonist Naltrindole aggregated 
      the ischemic injury. However, the level of BDNF remained unchanged in the cortex, 
      striatum and hippocampus at 24 hours after MCAO and did not change in response to 
      DOR activation or inhibition. MCAO decreased both total CREB and pCREB in the 
      striatum, but not in the cortex, while DOR inhibition promoted a further decrease 
      in total and phosphorylated CREB in the striatum and decreased pATF-1 expression 
      in the cortex. In addition, MCAO increased CD11b expression in the cortex, 
      striatum and hippocampus, and DOR activation specifically attenuated the ischemic 
      increase in the cortex but not in the striatum and hippocampus. CONCLUSIONS: DOR 
      activation rescues TrkB signaling by reversing ischemia/reperfusion induced 
      decrease in the full-length TrkB receptor and reduces brain injury in 
      ischemia/reperfusion.
FAU - Tian, Xuesong
AU  - Tian X
AD  - State Key Laboratory of Medical Neurobiology, Department of Integrative Medicine 
      and Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
FAU - Guo, Jingchun
AU  - Guo J
FAU - Zhu, Min
AU  - Zhu M
FAU - Li, Minwei
AU  - Li M
FAU - Wu, Gencheng
AU  - Wu G
FAU - Xia, Ying
AU  - Xia Y
LA  - eng
GR  - R01 AT004422/AT/NCCIH NIH HHS/United States
GR  - R01 HD034852/HD/NICHD NIH HHS/United States
GR  - AT-004422/AT/NCCIH NIH HHS/United States
GR  - HD-034852/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130702
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Activating Transcription Factor 1)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CD11b Antigen)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (TAN 67)
RN  - 5S6W795CQM (Naltrexone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - G167Z38QA4 (naltrindole)
SB  - IM
MH  - Activating Transcription Factor 1/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Brain/blood supply/drug effects/*metabolism
MH  - Brain Ischemia/complications/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - CD11b Antigen/metabolism
MH  - Cerebrovascular Circulation/drug effects
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Infarction, Middle Cerebral Artery/complications/metabolism
MH  - Male
MH  - Naltrexone/analogs & derivatives/pharmacology
MH  - Quinolines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*metabolism
MH  - Receptors, Opioid, delta/agonists/antagonists & inhibitors/*metabolism
MH  - Reperfusion Injury/etiology/*metabolism
PMC - PMC3699518
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/07/12 06:00
MHDA- 2014/02/08 06:00
PMCR- 2013/07/02
CRDT- 2013/07/12 06:00
PHST- 2011/11/07 00:00 [received]
PHST- 2013/06/13 00:00 [accepted]
PHST- 2013/07/12 06:00 [entrez]
PHST- 2013/07/12 06:00 [pubmed]
PHST- 2014/02/08 06:00 [medline]
PHST- 2013/07/02 00:00 [pmc-release]
AID - PONE-D-11-22093 [pii]
AID - 10.1371/journal.pone.0069252 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 2;8(7):e69252. doi: 10.1371/journal.pone.0069252. Print 2013.