Expression and Significance of Monocarboxylate Transporters in Cortex of Rats After Exercise-induced Fatigue

doi:10.12300/j.issn.1674-5817.2021-053

Abstract

Abstract:

Objective To explore the correlation between the adaptation of the body to exercise-induced fatigue and the expression of monocarboxylate transporters (MCTs) in the cerebral cortex. Methods A total of 42 SD rats were randomly divided into control group and fatigue group 1 to 6. Firstly, the average exhaustive times in each fatigue group were recorded to determine the trend of exercise-induced fatigue after 1, 3, 5, 7, 9 and 14 days exhaustive load treadmill exercises respectively. Subsequently, the changes of MCT1, MCT2 and MCT4 expression in cerebral motor cortex of rat brain were detected by Western blotting and double-labeling immunofluorescence. Results After 5 days of exercise, the average exhaustive time of rats in fatigue of group 3 reached the lowest level [(67.00±7.07) min] and it recovered to (89.17±9.45) min after 9 days of exercise, the difference was statistically significant (P<0.05). After that, the exercise ability of the rats remained basically constant. Western blotting analysis showed a small amount of MCT1, MCT2 and MCT4 normal expression in cerebral motor cortex of rats' brain in control group. After 5 days of exercise, the expression levels of MCT2 in fatigue of group 3 were significantly increased by 74.2% compared with the control group (P<0.05). After 7 days of exercise, the expression levels of MCT1 and MCT4 in fatigue of group 4 were significantly increased by 89.5% and 92.0% compared with the control group (P<0.05). After that, MCT1, MCT2, and MCT4 maintained high expression. The results of immunofluorescence were consistent with those of Western blotting. Conclusion The regulation of cerebral lactic acid metabolism represented by the increased expression of MCTs in the cerebral cortex is related to the adaptation of the body to exercise-induced fatigue, which can be used as a target for exercise-induced fatigue medical intervention.

Key words: Exercise-induced fatigue, Central fatigue, Monocarboxylate transporters, Cerebral cortex, Rats

CLC Number:

G804.7

Chen GAO,Wan WANG,Yurong LI,et al. Expression and Significance of Monocarboxylate Transporters in Cortex of Rats After Exercise-induced Fatigue[J]. Laboratory Animal and Comparative Medicine, 2022, 42(1): 42-47. DOI: 10.12300/j.issn.1674-5817.2021-053.

Figures/Tables 3

Table 1 The exhaustive time of rats in fatigue groups

组别	递增负荷运动天数/d	平均运动力竭时间/min
Fatigue 1	1	120.17±11.18^#△
Fatigue 2	3	81.17±10.57^*
Fatigue 3	5	67.00±7.07^*△
Fatigue 4	7	75.67±4.97^*
Fatigue 5	9	89.17±9.45^*#
Fatigue 6	14	91.17±11.43^*#

Figure 1 Expression of MCT1， MCT2 and MCT4 in cerebral motor cortex of rats in different groups detected by Western blotting

Figure 2 Expression of MCT1， MCT2 and MCT4 in cerebral motor cortex of rats in different groups detected by imunofluorescence（×400）

References 28

1	SECHER N H, QUISTORFF B, DALSGAARD M K. The muscles work, but the brain gets tired[J]. Ugeskr Laeger, 2006, 168(51):4503-4506.
2	AMANN M, ROMER L M, SUBUDHI A W, et al. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans[J]. J Physiol, 2007, 581(1):389-403. DOI:10.1113/jphysiol.2007.129700 .
3	DAVIS J M, BAILEY S P. Possible mechanisms of central nervous system fatigue during exercise[J]. Med Sci Sports Exerc, 1997, 29(1):45-57. DOI:10.1097/00005768-199701000-00008 .
4	刘红平, 杨国愉, 张晶轩, 等. 急进高原驻训军人躯体-脑力疲劳追踪研究[J]. 西北国防医学杂志, 2017, 38(9):565-569. DOI:10.16021/j.cnki.1007-8622.2017.09.002 .
5	SCHURR A, GOZAL E. Aerobic production and utilization of lactate satisfy increased energy demands upon neuronal activation in hippocampal slices and provide neuroprotection against oxidative stress[J]. Front Pharmacol, 2011, 2:96. DOI:10.3389/fphar.2011.00096 .
6	GAO C, ZHOU L Y, ZHU W X, et al. Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures[J]. Neurosci Lett, 2015, 594:99-104. DOI:10.1016/j.neulet.2015.03.062 .
7	DHILLON H S, DOSE J M, SCHEFF S W, et al. Time course of changes in lactate and free fatty acids after experimental brain injury and relationship to morphologic damage[J]. Exp Neurol, 1997, 146(1):240-249. DOI:10.1006/exnr.1997.6524 .
8	王静, 刘洪涛. 脑乳酸对运动性中枢疲劳的作用及影响[J]. 中国临床康复, 2004, 8(22):4572-4573.
9	HALESTRAP A P. The SLC16 gene family: structure, role and regulation in health and disease[J]. Mol Aspects Med, 2013, 34(2-3):337-349. DOI:10.1016/j.mam.2012.05.003 .
10	GAO C, ZHU W X, Tian L Z, et al. MCT4-mediated expression of EAAT1 is involved in the resistance to hypoxia injury in astrocyte-neuron co-cultures[J]. Neurochem Res, 2014, 40(4): 818-828. DOI: 10.1007/s11064-015-1532-2 .
11	PELLERIN L, PELLEGRI G, BITTAR P G, et al. Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle[J]. Dev Neurosci, 1998, 20(4-5):291-299. DOI:10.1159/000017324 .
12	SIMPSON I A, CARRUTHERS A, VANNUCCI S J. Supply and demand in cerebral energy metabolism: the role of nutrient transporters[J]. J Cereb Blood Flow Metab, 2007, 27(11):1766-1791. DOI:10.1038/sj.jcbfm.9600521 .
13	程泽鹏, 冯钰, 史仍飞. 运动过程中单羧酸转运蛋白(MCTs)作用的研究进展[J]. 军事体育学报, 2017, 36(3):89-94. DOI:10.3969/j.issn.1671-1300.2017.03.025
14	BEDFORD T G, TIPTON C M, WILSON N C, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures[J]. J Appl Physiol Respir Environ Exerc Physiol, 1979, 47(6):1278-1283. DOI:10.1152/jappl. 1979.47.6.1278 .
15	胡琰茹, 乔德才, 刘晓莉. 力竭运动过程中大鼠苍白球内侧部对皮层的调控作用[J]. 中国运动医学杂志, 2013, 32(5):420-425, 419. DOI:10.16038/j.1000-6710.2013.05.001 .
16	GAO C, WANG C, LIU B, et al. Intermittent hypoxia preconditioning-induced epileptic tolerance by upregulation of monocarboxylate transporter 4 expression in rat hippocampal astrocytes[J]. Neurochem Res, 2014, 39(11):2160-2169. DOI:10.1007/s11064-014-1411-2 .
17	ANDERSEN L W, MACKENHAUER J, ROBERTS J C, et al. Etiology and therapeutic approach to elevated lactate levels[J]. Mayo Clin Proc, 2013, 88(10):1127-1140. DOI:10.1016/j.mayocp.2013.06.012 .
18	GAO C, LI Z Y, BAI J, et al. Involvement of monocarboxylate transporters in the cross-tolerance between epilepsy and cerebral infarction: a promising choice towards new treatments[J]. Neurosci Lett, 2019, 707:134305. DOI:10.1016/j.neulet.2019.134305 .
19	郑庆云, 李世昌, 刘中刚. 运动对单羧酸转运蛋白的影响[J]. 中国临床康复, 2006, 10(44):155-157.
20	BROOKS G A. Cell-cell and intracellular lactate shuttles[J]. J Physiol, 2009, 587(Pt 23):5591-5600. DOI:10.1113/jphysiol. 2009.178350 .
21	CONTRERAS-BAEZA Y, SANDOVALP Y, ALARCON R, et al. Monocarboxylate transporter 4 (MCT4) is a high affinity transporter capable of exporting lactate in high-lactate microenvironments[J]. J Biol Chem, 2019, 294(52):20135-20147. DOI: 10.1074/jbc.RA119.009093 .
22	EYDOUX N, DUBOUCHAUD H, PY G, et al. Lactate transport in rat sarcolemmal vesicles after a single bout of submaximal exercise[J]. Int J Sports Med, 2000, 21(6):393-399. DOI:10.1055/s-2000-3830 .
23	CHIH C P, ROBERTS E L Jr. Energy substrates for neurons during neural activity: a critical review of the astrocyte-neuron lactate shuttle hypothesis[J]. J Cereb Blood Flow Metab, 2003, 23(11):1263-1281. DOI:10.1097/01.WCB.0000081369.51727.6F .
24	PELLERIN L. Lactate as a pivotal element in neuron-Glia metabolic cooperation[J]. Neurochem Int, 2003, 43(4-5):331-338. DOI:10.1016/S0197-0186(03)00020-2 .
25	WADA H, OKADA Y, UZUO T, et al. The effects of glucose, mannose, fructose and lactate on the preservation of neural activity in the hippocampal slices from the Guinea pig[J]. Brain Res, 1998, 788(1-2):144-150. DOI:10.1016/s0006-8993(97)01532-1 .
26	TAKATA T, OKADA Y. Effects of deprivation of oxygen or glucose on the neural activity in the Guinea pig hippocampal slice—intracellular recording study of pyramidal neurons[J]. Brain Res, 1995, 683(1):109-116. DOI:10.1016/0006-8993(95)00318-K .
27	TANAKA M, NAKAMURA F, MIZOKAWA S, et al. Role of lactate in the brain energy metabolism: revealed by Bioradiography[J]. Neurosci Res, 2004, 48(1):13-20. DOI:10.1016/j.neures.2003.09.001 .
28	张换鸽. 神经递质与运动性中枢疲劳[J]. 当代体育科技, 2012, 2(4):18-20. DOI:10.16655/j.cnki.2095-2813.2012.04.020 .

[1]	TANG Jianping, ZHAO Liya, ZHAO Ying. Screening and Analysis of Microsatellite Genetic Markers in Commonly Used Inbred Rat Strains [J]. Laboratory Animal and Comparative Medicine, 2026, 46(3): 388-396.
[2]	LI Jiafei, ZHANG Zhenhao, WANG Shuo, TIAN Ge, WEN Shuang, YAN Yuxue, CUI Ran, YE Zhen, CUI Yongchun. Effects of Autonomic Neuromodulators on Atrial Electrical Remodeling and Histopathological Changes in a Rat Model of Atrial Fibrillation [J]. Laboratory Animal and Comparative Medicine, 2026, 46(3): 321-331.
[3]	AI Xiufeng, ZHANG Lizong, FANG Mingsun, LÜ Dongying, CHEN Chu, CAI Zhaowei, WANG Dejun. Analysis of Differences in the Intestinal Flora of Rats and Mice after Drinking Chlorinated Water Based on 16S rRNA Sequencing [J]. Laboratory Animal and Comparative Medicine, 2026, 46(3): 437-445.
[4]	SONG Jing, YANG Zongtong, LI Xiaojing, LI Zifa, SU Fengyun, XU Dongchuan, SUI Zaiyun. Effects of Xiebai San on the Morphological Structures of Lung and Intestinal Tissues and Expression Levels of PI3K and Akt in Rats with Allergic Asthma [J]. Laboratory Animal and Comparative Medicine, 2026, 46(2): 191-204.
[5]	TANG Xiaohang, GU Yingmin, LÜ Yangyang, HUANG Mingshu, TIAN Xuesong. Evaluation of the Histological Staining Performance of Rat Eyeball Sections Prepared Using a Self-Developed Fixative [J]. Laboratory Animal and Comparative Medicine, 2026, 46(2): 261-270.
[6]	JIANG Haitao, YUAN Hantao, HUANG Wenting, YANG Rongrong, CHEN Xiaochun, YU Baoqing, LI Sibo. Regulation of Rat Intervertebral Disc Annulus Fibrosus Cell Proliferation and Apoptosis by Yaoshu Zhuyu Fang via miR-17-5P/MDM2/p53 Pathway [J]. Laboratory Animal and Comparative Medicine, 2026, 46(1): 55-65.
[7]	GAO Chaoqi, ZHU Zhibo, SUN Xiandong. Application Progress and Classification Analysis of Rat Vascular Remodeling Models [J]. Laboratory Animal and Comparative Medicine, 2025, 45(5): 542-550.
[8]	LUO Yifan, ZHANG Zhenwei, MEI Lu, SHI Yeping, XING Yitong, ZHANG Zeqi, LI Chuxin, HAN Chunxia, YANG Pingshun, CHEN Qiusheng. Telocytes-Mediated Effects and Mechanisms of Anointing and Massage Therapy Using Oligopeptide-Herbal Medicine Composite Against Obesity in Rats [J]. Laboratory Animal and Comparative Medicine, 2025, 45(5): 551-560.
[9]	QIN Chao, LI Shuangxing, ZHAO Tingting, JIANG Chenchen, ZHAO Jing, YANG Yanwei, LIN Zhi, WANG Sanlong, WEN Hairuo. Study on the 90-day Feeding Experimental Background Data of SD Rats for Drug Safety Evaluation [J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 439-448.
[10]	LIU Liyu, JI Bo, LIU Xiaoxuan, FANG Yang, ZHANG Ling, GUO Tingting, QUAN Ye, LI Hewen, LIU Yitian. Exploration of Rat Fetal Lung Tissue Fixation Methods [J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 432-438.
[11]	PAN Yicong, JIANG Wenhong, HU Ming, QIN Xiao. Optimization of Surgical Procedure and Efficacy Evaluation of Aortic Calcification Model in Rats with Chronic Kidney Disease [J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 279-289.
[12]	LIU Zhiwei, YANG Ran, LIAN Hao, ZHANG Yu, JIN Lilun. Cartilage Protection and Anti-Inflammatory Effects of Fraxetin on Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis [J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 259-268.
[13]	JIANG Meng, HAO Shulan, TONG Liguo, ZHONG Qiming, GAO Zhenfei, WANG Yonghui, WANG Xixing, JI Haijie. Dynamic Evaluation of Vinorelbine-Induced Phlebitis of Dorsalis Pedis Vein in a Rat Model [J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 251-258.
[14]	LIAN Hui, JIANG Yanling, LIU Jia, ZHANG Yuli, XIE Wei, XUE Xiaoou, LI Jian. Construction and Evaluation of a Rat Model of Abnormal Uterine Bleeding [J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 130-146.
[15]	YIN Yulian, MA Lina, TU Siyuan, CHEN Ling, YE Meina, CHEN Hongfeng. Establishment and Evaluation of a Rat Model of Non-Puerperal Mastitis [J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 587-596.