Neuronal and vascular deficits following chronic adaptation to high altitude

Nathan P. Cramer, Alexandru Korotcov, Asamoah Bosomtwi, Xiufen Xu, Derek R. Holman, Kathleen Whiting, Scott Jones, Andrew Hoy, Bernard J. Dardzinski, Zygmunt Galdzicki

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)293-304
Number of pages12
JournalExperimental Neurology
Volume311
DOIs
StatePublished - Jan 2019
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Cramer, N. P., Korotcov, A., Bosomtwi, A., Xu, X., Holman, D. R., Whiting, K., Jones, S., Hoy, A., Dardzinski, B. J., & Galdzicki, Z. (2019). Neuronal and vascular deficits following chronic adaptation to high altitude. Experimental Neurology, 311, 293-304. https://doi.org/10.1016/j.expneurol.2018.10.007