Neuronal and vascular deficits following chronic adaptation to high altitude
| Autor: | Alexandru Korotcov, Asamoah Bosomtwi, Derek Holman, Xiufen Xu, Nathan P. Cramer, Andrew R. Hoy, Scott R. Jones, Kathleen Whiting, Bernard J. Dardzinski, Zygmunt Galdzicki |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Hippocampus Mice Transgenic Neocortex Hippocampal formation Corpus callosum Amygdala Mice Random Allocation 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Animals Medicine Fear conditioning Neuroinflammation Neurons Memory Disorders business.industry Altitude Adaptation Physiological Mice Inbred C57BL Electrophysiology Atmospheric Pressure 030104 developmental biology medicine.anatomical_structure nervous system Neurology Cerebral blood flow Cerebrovascular Circulation business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Experimental Neurology. 311:293-304 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2018.10.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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