PMID- 28842826
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20220409
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 55
IP  - 1
DP  - 2018 Jan
TI  - Environmental Enrichment Reverses Tyrosine Kinase Inhibitor-Mediated Impairment 
      Through BDNF-TrkB Pathway.
PG  - 43-59
LID - 10.1007/s12035-017-0716-y [doi]
AB  - Exposure to an enriched environment (EE) has neuroprotective benefits and 
      improves recovery from brain injury due to, among other, increased neurotrophic 
      factor expression. Through these neurotrophins, important cortical and 
      hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell 
      receptors, among others, the vascular endothelial growth factor receptor (VEGFR). 
      Our aim was to investigate the effectiveness of EE counteracting cognitive and 
      cellular effects after tyrosine kinase receptor blockade. Animals were reared 
      under standard laboratory condition or EE; both groups received vandetanib or 
      vehicle. Visuospatial learning was tested with Morris water maze. Neuronal, 
      interneuronal, and vascular densities were measured by inmunohistochemistry and 
      histochemistry techniques. Quantifications were performed in the hippocampus and 
      in the visual cortex. Brain-derived neurotrophic factor (BDNF), tyrosine kinase B 
      receptor (TrkB), Akt, and Erk were measured by Western blot technique. Vandetanib 
      produces a significant decrease in vascular and neuronal densities and reduction 
      in the expression of molecules involved in survival and proliferation processes 
      such as phospho-Akt/Akt and phospho-Erk/Erk. These results correlated to a 
      cognitive impairment in visuospatial test. On the other hand, animals reared in 
      an EE are able to reverse the negative effects, activating PI3K-AKT and MAP 
      kinase pathways mediated by BDNF-TrkB binding. Present results provide novel and 
      consistent evidences about the usefulness of living in EE as a strategy to 
      improve deleterious effects of blocking neurotrophic pathways by vandetanib and 
      the notable role of the BDNF-TrkB pathway to balance the neurovascular unit and 
      cognitive effects.
FAU - Bengoetxea, Harkaitz
AU  - Bengoetxea H
AD  - Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of 
      Neuroscience, Faculty of Medicine and Surgery, University of the Basque Country 
      (UPV/EHU), 48940, Leioa, Bizkaia, Spain. harkaitz.bengoetxea@ehu.eus.
FAU - Rico-Barrio, Irantzu
AU  - Rico-Barrio I
AD  - Department of Neuroscience, Faculty of Medicine and Surgery, University of the 
      Basque Country (UPV/EHU), Barrio Sarriena, E-48940, Leioa, Bizkaia, Spain.
FAU - Ortuzar, Naiara
AU  - Ortuzar N
AD  - Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of 
      Neuroscience, Faculty of Medicine and Surgery, University of the Basque Country 
      (UPV/EHU), 48940, Leioa, Bizkaia, Spain.
FAU - Murueta-Goyena, Ane
AU  - Murueta-Goyena A
AD  - Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of 
      Neuroscience, Faculty of Medicine and Surgery, University of the Basque Country 
      (UPV/EHU), 48940, Leioa, Bizkaia, Spain.
FAU - Lafuente, Jose V
AU  - Lafuente JV
AD  - Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of 
      Neuroscience, Faculty of Medicine and Surgery, University of the Basque Country 
      (UPV/EHU), 48940, Leioa, Bizkaia, Spain.
AD  - Nanoneurosurgery Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, 
      Spain.
AD  - Faculty of Health Science, Universidad Autonoma de Chile, Santiago de Chile, 
      Chile.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - *Environment
MH  - Protein Kinase Inhibitors/*toxicity
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptor, trkB/*antagonists & inhibitors/*metabolism
MH  - Signal Transduction/drug effects/*physiology
OTO - NOTNLM
OT  - Enriched environment
OT  - Hippocampus
OT  - Neuroprotection
OT  - Neurotrophins
OT  - Tyrosine kinase inhibitor
OT  - Visual cortex
EDAT- 2017/08/27 06:00
MHDA- 2019/05/09 06:00
CRDT- 2017/08/27 06:00
PHST- 2017/08/27 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2017/08/27 06:00 [entrez]
AID - 10.1007/s12035-017-0716-y [pii]
AID - 10.1007/s12035-017-0716-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2018 Jan;55(1):43-59. doi: 10.1007/s12035-017-0716-y.