PMID- 22496799
OWN - NLM
STAT- MEDLINE
DCOM- 20120821
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 4
DP  - 2012
TI  - Propofol-induced changes in neurotrophic signaling in the developing nervous 
      system in vivo.
PG  - e34396
LID - 10.1371/journal.pone.0034396 [doi]
LID - e34396
AB  - Several studies have revealed a role for neurotrophins in anesthesia-induced 
      neurotoxicity in the developing brain. In this study we monitored the spatial and 
      temporal expression of neurotrophic signaling molecules in the brain of 
      14-day-old (PND14) Wistar rats after the application of a single propofol dose 
      (25 mg/kg i.p). The structures of interest were the cortex and thalamus as the 
      primary areas of anesthetic actions. Changes of the protein levels of the 
      brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), their 
      activated receptors tropomyosin-related kinase (TrkA and TrkB) and downstream 
      kinases Akt and the extracellular signal regulated kinase (ERK) were assessed by 
      Western immunoblot analysis at different time points during the first 24 h after 
      the treatment, as well as the expression of cleaved caspase-3 fragment. 
      Fluoro-Jade B staining was used to follow the appearance of degenerating neurons. 
      The obtained results show that the treatment caused marked alterations in levels 
      of the examined neurotrophins, their receptors and downstream effector kinases. 
      However, these changes were not associated with increased neurodegeneration in 
      either the cortex or the thalamus. These results indicate that in the brain of 
      PND14 rats, the interaction between Akt/ERK signaling might be one of important 
      part of endogenous defense mechanisms, which the developing brain utilizes to 
      protect itself from potential anesthesia-induced damage. Elucidation of the 
      underlying molecular mechanisms will improve our understanding of the 
      age-dependent component of anesthesia-induced neurotoxicity.
FAU - Popic, Jelena
AU  - Popic J
AD  - Department of Neurobiology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Pesic, Vesna
AU  - Pesic V
FAU - Milanovic, Desanka
AU  - Milanovic D
FAU - Todorovic, Smilja
AU  - Todorovic S
FAU - Kanazir, Selma
AU  - Kanazir S
FAU - Jevtovic-Todorovic, Vesna
AU  - Jevtovic-Todorovic V
FAU - Ruzdijic, Sabera
AU  - Ruzdijic S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120404
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Anesthetics, Intravenous/*pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Caspase 3/metabolism
MH  - Cerebral Cortex/cytology/drug effects/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hypothalamus/cytology/drug effects/metabolism
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nerve Growth Factor/metabolism
MH  - Nerve Growth Factors/*metabolism
MH  - Neurogenesis/*drug effects
MH  - Neurons/*cytology/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Propofol/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC3319585
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/04/13 06:00
MHDA- 2012/08/22 06:00
PMCR- 2012/04/04
CRDT- 2012/04/13 06:00
PHST- 2011/12/01 00:00 [received]
PHST- 2012/02/27 00:00 [accepted]
PHST- 2012/04/13 06:00 [entrez]
PHST- 2012/04/13 06:00 [pubmed]
PHST- 2012/08/22 06:00 [medline]
PHST- 2012/04/04 00:00 [pmc-release]
AID - PONE-D-11-23965 [pii]
AID - 10.1371/journal.pone.0034396 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(4):e34396. doi: 10.1371/journal.pone.0034396. Epub 2012 Apr 4.