Abstract
Professionals and mountaineers often face the problem of reperfusion injury due to re-oxygenation, upon their return to sea-level after sojourn at high altitude. Small conductance calcium-activated potassium channels (SK channels) have a role in regulating hippocampal synaptic plasticity. However, the role of SK channels under hypoxia-reoxygenation (H/R) is unknown. The present study hypothesized that SK channels play a significant role in H/R induced cognitive dysfunction. Sprague–Dawley rats were exposed to simulated HH (25,000 ft) continuously for 7 days followed by reoxygenation periods 3, 6, 24, 48, 72 and 120 h. It was observed that H/R exposure caused impairment in spatial memory as indicated by increased latency (p < 0.001) and pathlength (p < 0.001). The SK1 channel expression increased upon HH exposure (102.89 ± 7.055), which abrogated upon reoxygenation. HH exposure results in an increase in SK2 (CA3, 297.67 ± 6.69) and SK3 (CA1, 246 ± 5.13) channels which continued to increase gradually upon reoxygenation. The number of pyknotic cells (24 ± 2.03) (p < 0.01) and the expression of caspase-3 increased with HH exposure, which continued in the reoxygenation group (177.795 ± 1.264). Similar pattern was observed in lipid peroxidation (p < 0.001), LDH activity (p < 0.001) and ROS production (p < 0.001). A positive correlation of memory, cell death and oxidative stress indicates that H/R exposure increases oxidative stress coupled with SK channel expression, which may play a role in H/R-induced cognitive decline and neurodegeneration.
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This work was supported by Grant [No: DIP-263 (NK)] from DRDO, Ministry of Defence, Government of India. NK and MK received fellowship from DRDO, India.
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NK conceived and coordinated the study, assisted in data analysis. MK designed the study, performed and analyzed the experiments. MK, NK wrote the manuscript. NK, SP contributed with hypobaric hypoxia exposures. DP, BK and UP helped in administrative processing of the manuscript and reviewed the manuscript before submission. All authors have read and approved the final version of the manuscript.
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Kadam, M., Perveen, S., Kushwah, N. et al. Elucidating the role of hypoxia/reoxygenation in hippocampus-dependent memory impairment: do SK channels play role?. Exp Brain Res 239, 1747–1763 (2021). https://doi.org/10.1007/s00221-021-06095-8
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DOI: https://doi.org/10.1007/s00221-021-06095-8