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High-altitude cognitive impairment is prevented by enriched environment including exercise via VEGF signaling

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dc.contributor.author Koester-Hegmann, C.
dc.contributor.author Bengoetxea, H.
dc.contributor.author Kosenkov, D.
dc.contributor.author Thiersch, M.
dc.contributor.author Haider, T.
dc.contributor.author Gassmann, M.
dc.contributor.author Schneider Gasser, E.M.
dc.date.accessioned 2019-12-06T21:02:56Z
dc.date.available 2019-12-06T21:02:56Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/7506
dc.description.abstract Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here we show that high-altitude exposure (3540 m asl) of Long Evans rats during early adulthood (P48–P59) increases brain microvasculature and neurogenesis but impairs spatial and visual memory along with an increase in neuronal apoptosis. We tested whether enriched environment including a running wheel for voluntary exercise (EE) can prevent cognitive impairment at high-altitude and whether apoptosis is prevented. We found that EE retained spatial and visual memory at high altitude, and prevented neuronal apoptosis. Further, we tested whether vascular endothelial growth factor (VEGF) signaling is required for the EE-mediated recovery of spatial and visual memory and the reduction in apoptosis. Pharmacological inhibition of VEGF signaling by oral application of a tyrosine kinase inhibitor (Vandetanib) prevented the recovery of spatial and visual memory in animals housed in EE, along with an increase in apoptosis and a reduction in neurogenesis. Surprisingly, inhibition of VEGF signaling also caused impairment in spatial memory in EE-housed animals reared at low altitude, affecting mainly dentate gyrus microvasculature but not neurogenesis. We conclude that EE-mediated VEGF signaling is neuroprotective and essential for the maintenance of cognition and neurogenesis during high-altitude exposure, and for the maintenance of spatial memory at low altitude. Finally, our data also underlines the potential risk of cognitive impairment and disturbed high altitude adaption from the use of VEGF-signaling inhibitors for therapeutic purposes. en_US
dc.language.iso eng
dc.publisher Frontiers Media
dc.relation.ispartof urn:issn:1662-5102
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject altitude en_US
dc.subject angiogenesis en_US
dc.subject Angiogenesis en_US
dc.subject animal experiment en_US
dc.subject animal model en_US
dc.subject animal tissue en_US
dc.subject Article en_US
dc.subject behavior assessment en_US
dc.subject brain perfusion en_US
dc.subject cholinesterase en_US
dc.subject cognition en_US
dc.subject cognitive defect en_US
dc.subject controlled study en_US
dc.subject environment en_US
dc.subject exercise en_US
dc.subject exposure en_US
dc.subject hematocrit en_US
dc.subject hippocampus en_US
dc.subject hypobarism en_US
dc.subject hypoxia en_US
dc.subject imaging en_US
dc.subject immunofluorescence en_US
dc.subject immunohistochemistry en_US
dc.subject male en_US
dc.subject microvasculature en_US
dc.subject nervous system development en_US
dc.subject neuroapoptosis en_US
dc.subject Neurogenesis en_US
dc.subject neuroprotection en_US
dc.subject Neuroprotection en_US
dc.subject nonhuman en_US
dc.subject object displacement test en_US
dc.subject object replacement test en_US
dc.subject rat en_US
dc.subject sham procedure en_US
dc.subject signal transduction en_US
dc.subject spatial memory en_US
dc.subject Spatial memory en_US
dc.subject stereology en_US
dc.subject Tyrosine kinase inhibitor en_US
dc.subject vandetanib en_US
dc.subject vasculotropin en_US
dc.subject visual memory en_US
dc.subject Visual memory en_US
dc.title High-altitude cognitive impairment is prevented by enriched environment including exercise via VEGF signaling en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3389/fncel.2018.00532
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.04

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