ArticleFrontiers in cellular neuroscience2018
High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling.
Article in Frontiers in cellular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Can Environmental Enrichment Mitigate Cell Apoptosis in the Central Nervous System Under Adverse Health Conditions? A Systematic Review.Clinical and translational science · 2026Pooled it
- High altitude limits the biogeography of common rats but not house mice.Scientific reports · 2026Article
- Newborn brain development comparison of plateau and plain regions: insights from quantitative EEG.Pediatric research · 2026Article
- Chronic hypoxia reshapes the brain: subregional volume reductions of the hippocampus and amygdala contrasts with behavioral resilience in long-term high-altitude migrants.Frontiers in neuroscience · 2026Article
- Pro-Inflammatory Microglia Exacerbate High-Altitude-Induced Cognitive Impairment by Driving Lipid Droplet Accumulation in Astrocytes.Antioxidants (Basel, Switzerland) · 2025Article
- Aerobic exercise training improves learning and memory performance in hypoxic-exposed rats by activating the hippocampal PKA-CREB-BDNF signaling pathway.BMC neuroscience · 2025Article
- Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids.Frontiers in neuroscience · 2025Review
- Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation.Frontiers in aging neuroscience · 2025Article
- Nitronyl Nitroxide Ameliorates Hypobaric Hypoxia-Induced Cognitive Impairment in Mice by Suppressing the Oxidative Stress, Inflammatory Response and Apoptosis.Neurochemical research · 2024Article
- Association of altitude and frailty in Chinese older adults: using a cumulative frailty index model.Frontiers in public health · 2024Article
- A Continuous Extension of Gene Set Enrichment Analysis Using the Likelihood Ratio Test Statistics Identifies Vascular Endothelial Growth Factor as a Candidate Pathway for Alzheimer's Disease via ITGA5.Journal of Alzheimer's disease : JAD · 2024Article
- Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice.Neuroscience bulletin · 2024Article
- Exercise Reshapes the Brain: Molecular, Cellular, and Structural Changes Associated with Cognitive Improvements.Molecular neurobiology · 2023Review
- Exercise performance reduction and preventive measures in highland sports.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- The Oxygen Cascade from Atmosphere to Mitochondria as a Tool to Understand the (Mal)adaptation to Hypoxia.International journal of molecular sciences · 2023Review
- CX3CL1/CX3CR1 signal mediates M1-type microglia and accelerates high-altitude-induced forgetting.Frontiers in cellular neuroscience · 2023Article
- Effect of a combined program of running exercise and environmental enrichment on memory function and neurogenesis markers in amyloid-beta-induced Alzheimer-like model.Iranian journal of basic medical sciences · 2023Article
- High-altitude cerebral hypoxia promotes mitochondrial dysfunction and apoptosis of mouse neurons.Frontiers in molecular neuroscience · 2023Article
- Mechanism, prevention and treatment of cognitive impairment caused by high altitude exposure.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.