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Exp Neurol. 2019 Jan;311:293-304. doi: 10.1016/j.expneurol.2018.10.007. Epub 2018 Oct 13.

Neuronal and vascular deficits following chronic adaptation to high altitude.

Author information

1
Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Center for Neuroscience and Regenerative Medicine, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
2
Center for Neuroscience and Regenerative Medicine, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Department of Radiology and Radiological Sciences, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
3
Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Molecular & Cell Biology Graduate Program, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, MD, United States.
4
Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Neuroscience Graduate Program, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
5
Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Center for Neuroscience and Regenerative Medicine, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States; Molecular & Cell Biology Graduate Program, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, MD, United States; Neuroscience Graduate Program, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States. Electronic address: zgaldzicki@usuhs.edu.

Abstract

We sought to understand the mechanisms underlying cognitive deficits that are reported to affect non-native subjects following their prolonged stay and/or work at high altitude (HA). We found that mice exposed to a simulated environment of 5000 m exhibit deficits in hippocampal learning and memory accompanied by abnormalities in brain MR imaging. Exposure (1-8 months) to HA led to an increase in brain ventricular volume, a reduction in relative cerebral blood flow and changes in diffusion tensor imaging (DTI) derived parameters within the hippocampus and corpus callosum. Furthermore, neuropathological examination revealed significant expansion of the neurovascular network, microglia activation and demyelination within the corpus callosum. Electrophysiological recordings from the corpus callosum indicated that axonal excitabilities are increased while refractory periods are longer despite a lack of change in action potential conduction velocities of both myelinated and unmyelinated fibers. Next generation RNA-sequencing identified alterations in hippocampal and amygdala transcriptome signaling pathways linked to angiogenesis, neuroinflammation and myelination. Our findings reveal that exposure to hypobaric-hypoxia triggers maladaptive responses inducing cognitive deficits and suggest potential mechanisms underlying the adverse impacts of staying or traveling at high altitude.

KEYWORDS:

Action potential conductance; Angiogenesis; Corpus callosum; Cxcl12//SDF1; Fear-conditioning; Hypobaric-hypoxia; MRI; Memory; Neuroinflammation; Novel-object recognition; RNA-Seq; Real-time PCR

PMID:
30321497
DOI:
10.1016/j.expneurol.2018.10.007
[Indexed for MEDLINE]
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