PMID- 26649423
OWN - NLM
STAT- MEDLINE
DCOM- 20160628
LR  - 20160217
IS  - 1528-1175 (Electronic)
IS  - 0003-3022 (Linking)
VI  - 124
IP  - 3
DP  - 2016 Mar
TI  - Epigenetic Manipulation of Brain-derived Neurotrophic Factor Improves Memory 
      Deficiency Induced by Neonatal Anesthesia in Rats.
PG  - 624-40
LID - 10.1097/ALN.0000000000000981 [doi]
AB  - BACKGROUND: Although neonatal exposure to anesthetic drugs is associated with 
      memory deficiency in rodent models and possibly in pediatric patients, the 
      underlying mechanisms remain elusive. The authors tested their hypothesis that 
      exposure of the developing brain to anesthesia triggers epigenetic modification, 
      involving the enhanced interaction among transcription factors (histone 
      deacetylase 2, methyl-cytosine-phosphate-guanine-binding protein 2, and DNA 
      methyltransferase 1) in Bdnf promoter region(s) that inhibit brain-derived 
      neurotrophic factor (BDNF) expression, resulting in insufficient drive for local 
      translation of synaptic mRNAs. The authors further hypothesized that noninvasive 
      environmental enrichment (EE) will attenuate anesthesia-induced epigenetic 
      inhibition of BDNF signaling and memory loss in rodent models. METHODS: Seven 
      days after birth (P7), neonatal rats were randomly assigned to receive either 
      isoflurane anesthesia for 6 h or sham anesthesia. On P21, pups were weaned, and 
      animals were randomly assigned to EE or a standard cage environment (no EE). 
      Behavioral, molecular, and electrophysiological studies were performed on rats on 
      P65. RESULTS: The authors found a substantial reduction of hippocampal BDNF (n = 
      6 to 7) resulting from the transcriptional factors-mediated epigenetic 
      modification in the promoter region of Bdnf exon IV in rats exposed postnatally 
      to anesthetic drugs. This BDNF reduction led to the insufficient drive for the 
      synthesis of synaptic proteins (n = 6 to 8), thus contributing to the hippocampal 
      synaptic (n = 8 to 11) and cognitive dysfunction (n = 10) induced by neonatal 
      anesthesia. These effects were mitigated by the exposure to an enriched 
      environment. CONCLUSIONS: The findings of this study elucidated the epigenetic 
      mechanism underlying memory deficiency induced by neonatal anesthesia and propose 
      EE as a potential therapeutic approach.
FAU - Wu, Jiang
AU  - Wu J
AD  - From the Department of General Anesthesia, Anesthesiology Institute, Cleveland 
      Clinic, Cleveland, Ohio.
FAU - Bie, Bihua
AU  - Bie B
FAU - Naguib, Mohamed
AU  - Naguib M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Anesthesia, General/*adverse effects
MH  - Anesthetics, Inhalation/administration & dosage/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*genetics
MH  - Epigenesis, Genetic/drug effects/genetics
MH  - Epigenomics/*methods
MH  - Hippocampus
MH  - Injections, Intraventricular
MH  - Isoflurane/administration & dosage/toxicity
MH  - Male
MH  - Memory Disorders/*chemically induced/*genetics/therapy
MH  - Organ Culture Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2015/12/10 06:00
MHDA- 2016/06/29 06:00
CRDT- 2015/12/10 06:00
PHST- 2015/12/10 06:00 [entrez]
PHST- 2015/12/10 06:00 [pubmed]
PHST- 2016/06/29 06:00 [medline]
AID - 10.1097/ALN.0000000000000981 [doi]
PST - ppublish
SO  - Anesthesiology. 2016 Mar;124(3):624-40. doi: 10.1097/ALN.0000000000000981.