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Open AccessArticle

Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage

1
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
2
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Korea
3
Department of Emergency Medicine, Institute of Medical Sciences, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Korea
4
Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan, Gyeongnam 50510, Korea
5
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentis try, Gangnung-Wonju National University, Gangneung, Gangwon 25457, Korea
6
Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Korea
7
Department of Food Science and Nutrition, College of Natural Sciences, Hallym University, Chuncheon, Gangwon 24252, Korea
8
Department of Physical Education, College of Natural Science, Hallym University, Chuncheon, Gangwon 24252, Korea
9
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea
*
Authors to whom correspondence should be addressed.
These two authors have contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 644; https://doi.org/10.3390/ijms22020644
Received: 8 December 2020 / Revised: 6 January 2021 / Accepted: 6 January 2021 / Published: 11 January 2021
(This article belongs to the Section Molecular Biology)
Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood–brain barrier, which triggers gliosis after ischemic insults. View Full-Text
Keywords: intermittent fasting; ischemia-reperfusion; calcium binding protein; hippocampal CA1 region; pyramidal neurons intermittent fasting; ischemia-reperfusion; calcium binding protein; hippocampal CA1 region; pyramidal neurons
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MDPI and ACS Style

Sim, H.; Lee, T.-K.; Yoo, Y.H.; Ahn, J.H.; Kim, D.W.; Kim, B.; Lee, J.-C.; Park, J.H.; Lim, S.-S.; Park, J.-S.; Kang, I.J.; Kim, Y.-M.; Shin, M.C.; Cho, J.H.; Park, Y.; Won, M.-H. Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage. Int. J. Mol. Sci. 2021, 22, 644. https://doi.org/10.3390/ijms22020644

AMA Style

Sim H, Lee T-K, Yoo YH, Ahn JH, Kim DW, Kim B, Lee J-C, Park JH, Lim S-S, Park J-S, Kang IJ, Kim Y-M, Shin MC, Cho JH, Park Y, Won M-H. Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage. International Journal of Molecular Sciences. 2021; 22(2):644. https://doi.org/10.3390/ijms22020644

Chicago/Turabian Style

Sim, Hyejin; Lee, Tae-Kyeong; Yoo, Yeon H.; Ahn, Ji H.; Kim, Dae W.; Kim, Bora; Lee, Jae-Chul; Park, Joon H.; Lim, Soon-Sung; Park, Jung-Seok; Kang, Il J.; Kim, Young-Myeong; Shin, Myoung C.; Cho, Jun H.; Park, Yoonsoo; Won, Moo-Ho. 2021. "Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage" Int. J. Mol. Sci. 22, no. 2: 644. https://doi.org/10.3390/ijms22020644

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