Effect of Exercise Duration on Klotho and GluN2B Gene Expressions in Hippocampus of Wistar Rats with Moderate Intensity Exercise

Hanna Goenawan, Bela Ita Karina, Titing Nurhayati, Julia Windi Gunadi, Setiawan Setiawan, Ronny Lesmana


Exercise could delay the degeneration process by increasing Klotho, which is an endogen antioxidant. Klotho protects against oxidative damages, regulates hippocampal synaptic plasticity, and enhances GluN2B expression. This study aimed to analyze the effect of 14-day and 8-week moderate-intensity exercise on Klotho and GluN2B mRNA expressions in rat hippocampus. This study was an animal experimental study using Wistar rats that was performed from June to September 2019 at the Central Laboratory, Universitas Padjadjaran, Indonesia. Rats were divided into 4 groups: control (14-day control and 8-week control) and exercise group (14-day exercise and 8-week exercise).  The exercise groups ran at a moderate intensity (20m/min) for 30min/day, 5x/week. Hippocampus was then subjected to klotho and GluN2B gene expression analysis. The exercise groups showed a higher Klotho expression, both in 14 days (0.844±0.124 vs. 1.057±0.013) and 8 weeks (0.897±0.072 vs. 1.380±0.168) although statistically insignificant (p=0.24). No difference in GluN2B gene expression was observed between control and exercise groups on 14 days (1±0.09 vs. 1.22±0.09) and 8 weeks (1.24±0.03 vs. 1.38±0.05; p=0.11). In conclusion, 14-day and 8-week moderate-intensity exercise did not alter Klotho and GluN2B expressions in rat hippocampus.


Pengaruh Durasi Olahraga terhadap Perubahan Ekspresi Gen Klotho dan GluN2B di Hipokampus Tikus Galur Wistar yang Mendapatkan Perlakuan Lari Intensitas Sedang

Olahraga dapat menghambat proses degenerasi saraf dengan meningkatkan salah satu antioksidan endogen, yaitu Klotho. Klotho dapat melindungi sel neuron dari kerusakan oksidatif dan meningkatkan sinaptik plasticity pada hipokampus.  Penelitian ini bertujuan untuk melihat pengaruh olahraga lari pada hewan coba pada 14 hari dan 8 minggu terhadap perubahan ekspresi gen Klotho and GluN2B di hipokampus. Penelitian ini merupakan penelitian eksperimental dilaksanakan pada bulan Juni hingga September 2019 di Laboratorium Sentral Universitas Padjadjaran. Penelitian ini menggunakan tikus jantan galur wistar. Tikus dibagi menjadi 4 kelompok perlakuan dan kontrol. Olahraga dilakukan dengan treadmill tikus, kecepatan 20m/min, 30 menit perhari selama 5 kali perminggu. Kemudian, mRNA otak digunakan untuk PCR dengan menggunakan primer klotho dan GluN2B. Hasil penelitian menunjukkan bahwa tidak terdapat perbedaan yang bermakna (p=0.24) pada ekspresi gen Klotho pada 14 hari (0.844±0.124 vs 1.057±0.013) dan 8 minggu (0.897±0.072 vs 1.380±0.168) antara kelompok kontrol dan kelompok lari. Ekspresi gen dari GluN2B juga tidak menunjukkan perbedaan yang signifikan (p=0.11) pada 14 hari (1±0.09 vs 1.22±0.09)  dan 8 minggu (1.24±0.03 vs 1.38 ± 0.05). Simpulan, bahwa 8 minggu olahraga tidak meningkatan ekspresi Klotho dan GluN2B yang signifikan


Duration, Exercise, GluN2B, hippocampus, Klotho

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GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18(1): 88–106.

Schimidt HL, Garcia A, Izquierdo I, Mello-Carpes PB, Carpes FP. Strength training and running elicit different neuroprotective outcomes in a β-amyloid peptide-mediated Alzheimer’s disease model. Physiol Behav. 2019;206:206–12.

Kurucz A, Bombicz M, Kiss R, Priksz D, Varga B, Hortobágyi T, et al. Heme Oxygenase-1 activity as a correlate to exercise-mediated amelioration of cognitive decline and neuropathological alterations in an aging rat model of dementia. Biomed Res Int. 2018;2018(7212861):1-13.

Zeldich E, Harris DA, Liang J, Abraham CR, Tucker Zhou TB, Chen C-D, et al. The neuroprotective effect of klotho is mediated via regulation of members of the redox system. J Biol Chem. 2014;289(35):24700–15.

Li Q, Vo HT, Wang J, Fox-Quick S, Dobrunz LE, King GD. Klotho regulates CA1 hippocampal synaptic plasticity. Neuroscience. 2017;347: 123–33.

Foster PP, Rosenblatt KP, Kuljiš RO. Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front Neurol. 2011;2(28):1–15.

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, et al. Life extension factor klotho enhances cognition. Cell Rep. 2014;7(4):1065–76.

Hu F, Lao K, Luan J, Ji N, Wang W, Lv B, et al. Aerobic exercise stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney. Exp Ther Med. 2018;16(4):3511–7.

Ren H, Yu X, Yu L, Zhang GY, Xie FH, Shi N et al. Effects of different training loads on emotional state and mRNA and protein expressions of N-Methyl-D-Aspartate receptor subunits, postsynaptic density 95, and kinesin family member 17 in hippocampus of rats. Med Sci Monit. 2017; 23: 4954–60.

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, et al. Life extension factor klotho enhances cognition. Cell Rep.2014;7(4):1065–76.

Ho VM, Lee J-A, Martin KC. The cell biology of synaptic plasticity. Science. 2011;334(6056):623–8.

Lesmana R, Iwasaki T, Iizuka Y, Amano I, Shimokawa N, Koibuchi N. The change in thyroid hormone signaling by altered training intensity in male rat skeletal muscle. Endocr J. 2016;63(8):727–38.

Rios R, Pineda C, Lopez I, Muñoz-Castañeda J, Rodriguez M, Aguilera-Tejero E, et al. Phosphorus restriction does not prevent the increase in fibroblast growth factor 23 elicited by high fat diet. PLoS ONE. 2018;13(6): e0198481.

Ji Y, Bai G, Cao G, and Traub RJ. Estradiol modulates visceral hyperalgesia by increasing thoracolumbar spinal GluN2B subunit activity in female rats. Neurogastroenterol Motil. 2015;27(6):775–86.

Parker L, Mcguckin TA, Leicht AS. Influence of exercise intensity on systemic oxidative stress and antioxidant capacity. Clin Physiol Funct Imaging. 2014;34(5):377–83.

Ung L, Pattamatta U, Carnt N, Wilkinson-Berka JL, Liew G, White AJR. Oxidative stress and reactive oxygen species: A review of their role in ocular disease. Clin Sci. 2017;131(24):2865–83.

Brobey RK, Dheghani M, Foster PP, Kuro-O M, Rosenblatt KP. Klotho regulates 14-3-3ζ monomerization and binding to the ask1 signaling complex in response to oxidative stress. pLoS One. 2015;10(10):1–18.

Ji N, Luan J, Hu F, Zhao Y, Bosen Lv, Wang W, et al. Aerobic exercise-stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney. Exp Ther Med. 2018;16(4):3511–7.

Ramez M, Rajabi H, Ramezani F, Naderi N, Darbandi-Azar A, Nasirinez F. The greater effect of high-intensity interval training versus moderate-intensity continuous training on cardioprotection against ischemia-reperfusion injury through Klotho levels and attenuate of myocardial TRPC6 expression. BMC Cardiovasc Disord. 2019;19:118.

Joon-Ki Park, Sam-Jun Lee, Tae-Won Kim. Treadmill exercise enhances NMDA receptor expression in schizophrenia mice. Exerc Rehabil. 2014;10(1):15–21.

DOI: https://doi.org/10.15395/mkb.v52n3.2026

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