PMID- 24553857
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20220318
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 50
IP  - 3
DP  - 2014 Dec
TI  - Epigenetic enhancement of brain-derived neurotrophic factor signaling pathway 
      improves cognitive impairments induced by isoflurane exposure in aged rats.
PG  - 937-44
LID - 10.1007/s12035-014-8659-z [doi]
AB  - Isoflurane-induced cognitive impairments are well documented in animal models; 
      yet, the molecular mechanisms remain largely to be determined. In the present 
      study, 22-month-old male Sprague-Dawley rats received 2 h of 1.5 % isoflurane or 
      100 % oxygen daily for 3 consecutive days. For the intervention study, the rats 
      were intraperitoneally injected with 1.2 g/kg sodium butyrate 2 h before 
      isoflurane exposure. Our data showed that repeated isoflurane exposure 
      significantly decreased the freezing time to context and the freezing time to 
      tone in the fear conditioning test, which was associated with upregulated histone 
      deacetylase 2, reduced histone acetylation, and increased inflammation and 
      apoptosis in the hippocampus, and impairments of brain-derived neurotrophic 
      factor (BDNF)-tyrosine kinase receptor B (TrkB) and the downstream signaling 
      pathway phospho-calmodulin-dependent protein kinase and phospho-cAMP response 
      element-binding protein. These results suggest that isoflurane-induced cognitive 
      impairments are associated with the declines in chromatin histone acetylation and 
      the resulting downregulation of BDNF-TrkB signaling pathway. Moreover, the 
      cognitive impairments and the signaling deficits can be rescued by histone 
      deacetylase inhibitor sodium butyrate. Therefore, epigenetic enhancement of 
      BDNF-TrkB signaling may be a promising strategy for reversing isoflurane-induced 
      cognitive impairments.
FAU - Ji, MuHuo
AU  - Ji M
AD  - Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Dong, Lin
AU  - Dong L
FAU - Jia, Min
AU  - Jia M
FAU - Liu, WenXue
AU  - Liu W
FAU - Zhang, MingQiang
AU  - Zhang M
FAU - Ju, LinSha
AU  - Ju L
FAU - Yang, JiaoJiao
AU  - Yang J
FAU - Xie, Zhongcong
AU  - Xie Z
FAU - Yang, JianJun
AU  - Yang J
LA  - eng
GR  - R01 AG041274/AG/NIA NIH HHS/United States
GR  - R01 GM088801/GM/NIGMS NIH HHS/United States
GR  - R21 AG029856/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140221
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Aging/genetics/metabolism
MH  - Animals
MH  - Association Learning/physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognition Disorders/chemically induced/*genetics/metabolism
MH  - Conditioning, Classical/physiology
MH  - *Epigenesis, Genetic
MH  - Fear
MH  - Hippocampus/*metabolism
MH  - Isoflurane
MH  - Male
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*genetics
PMC - PMC4141042
MID - NIHMS586025
COIS- The authors declare no conflict of interest.
EDAT- 2014/02/21 06:00
MHDA- 2015/07/15 06:00
PMCR- 2015/03/01
CRDT- 2014/02/21 06:00
PHST- 2013/12/20 00:00 [received]
PHST- 2014/02/06 00:00 [accepted]
PHST- 2014/02/21 06:00 [entrez]
PHST- 2014/02/21 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - 10.1007/s12035-014-8659-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2014 Dec;50(3):937-44. doi: 10.1007/s12035-014-8659-z. Epub 2014 
      Feb 21.