Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death in the gerbil hippocampus by increasing NMDAR1 expression

Kim,Bora; Ahn,Ji Hyeon; Kim,Dae Won; Lee,Tae-Kyeong; Kim,Yoon Sung; Shin,Myoung Cheol; Cho,Jun Hwi; Kim,Young-Myeong; Park,Joon Ha; Kang,Il Jun; Lee,Jae-Chul; Won,Moo-Ho

doi:10.3892/mmr.2021.11895

Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death in the gerbil hippocampus by increasing NMDAR1 expression

Authors:
- Bora Kim
- Ji Hyeon Ahn
- Dae Won Kim
- Tae-Kyeong Lee
- Yoon Sung Kim
- Myoung Cheol Shin
- Jun Hwi Cho
- Young-Myeong Kim
- Joon Ha Park
- Il Jun Kang
- Jae-Chul Lee
- Moo-Ho Won
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Affiliations: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung‑Wonju National University, Gangneung, Gangwon 25457, Republic of Korea, Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea, Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Republic of Korea, Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea
Published online on: February 4, 2021 https://doi.org/10.3892/mmr.2021.11895
Article Number: 256
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Altered expression levels of N‑methyl‑D‑aspartate receptor (NMDAR), a ligand‑gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI‑induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post‑tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post‑tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI‑induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.

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