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Environmental enrichment reverses tyrosine kinase inhibitor-mediated impairment through BDNF-TrkB pathway

dc.contributor.authorBengoetxea H.
dc.contributor.authorRico-Barrio I.
dc.contributor.authorOrtuzar N.
dc.contributor.authorMurueta-Goyena A.
dc.contributor.authorLafuente J.V.
dc.date.accessioned2020-09-02T22:13:06Z
dc.date.available2020-09-02T22:13:06Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0716-y
dc.identifier.citation55, 1, 43-59
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3731
dc.descriptionExposure 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. © Springer Science+Business Media, LLC 2017.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectEnriched environment
dc.subjectHippocampus
dc.subjectNeuroprotection
dc.subjectNeurotrophins
dc.subjectTyrosine kinase inhibitor
dc.subjectVisual cortex
dc.subjectbrain derived neurotrophic factor
dc.subjectbrain derived neurotrophic factor receptor
dc.subjectcalbindin
dc.subjectcalretinin
dc.subjectmitogen activated protein kinase
dc.subjectparvalbumin
dc.subjectprotein kinase B
dc.subjectprotein tyrosine kinase inhibitor
dc.subjectsomatostatin
dc.subjectvandetanib
dc.subjectBdnf protein, rat
dc.subjectbrain derived neurotrophic factor
dc.subjectbrain derived neurotrophic factor receptor
dc.subjectprotein kinase inhibitor
dc.subjectprotein tyrosine kinase
dc.subjectTrkB protein, rat
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbrain region
dc.subjectcell density
dc.subjectcell proliferation
dc.subjectcell survival
dc.subjectcognition
dc.subjectcognitive defect
dc.subjectcontrolled study
dc.subjectdentate gyrus
dc.subjectenvironmental enrichment
dc.subjecthippocampus
dc.subjectimmunohistochemistry
dc.subjectMAPK signaling
dc.subjectMorris water maze test
dc.subjectnerve cell
dc.subjectnonhuman
dc.subjectprotein binding
dc.subjectprotein function
dc.subjectquantitative analysis
dc.subjectrat
dc.subjectsignal transduction
dc.subjectspatial learning
dc.subjectstereology
dc.subjectvisual cortex
dc.subjectWestern blotting
dc.subjectanimal
dc.subjectantagonists and inhibitors
dc.subjectdrug effect
dc.subjectenvironment
dc.subjectLong Evans rat
dc.subjectmetabolism
dc.subjectphysiology
dc.subjectsignal transduction
dc.subjectAnimals
dc.subjectBrain-Derived Neurotrophic Factor
dc.subjectEnvironment
dc.subjectProtein Kinase Inhibitors
dc.subjectProtein-Tyrosine Kinases
dc.subjectRats
dc.subjectRats, Long-Evans
dc.subjectReceptor, trkB
dc.subjectSignal Transduction
dc.titleEnvironmental enrichment reverses tyrosine kinase inhibitor-mediated impairment through BDNF-TrkB pathway
dc.typeArticle


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