Changes in Expression of Monocarboxylate Transporters in the Rat Cerebral Cortex after Exercise-induced Fatigue Under Simulated High-altitude Hypoxia and its Significance

doi:10.12300/j.issn.1674-5817.2022.050

Abstract

Abstract:

Objective To explore the correlation between adaptation to exercise-induced fatigue and lactate transport and metabolism in the cerebral cortex under high-altitude hypoxia. Methods A total of 63 SD rats were randomly divided into control, normal exercise, rush-entry-into-altitude, 3-day-altitude acclimatization, 1-week-altitude acclimatization, 2-week-altitude acclimatization, and monocarboxylate-transporter-inhibitor (altitude inhibitor injection) groups. Except for the control group, rats were subjected to exhaustive-load treadmill exercises under either normal pressure and normoxic conditions or low pressure and hypoxic conditions. The average time-to-exhaustion was used to determine variation trends in exercise-induced fatigue. The expression of monocarboxylate transporters (MCT)2 and MCT4 in the cerebral motor cortex was detected using western blotting and immunohistochemistry. The pathological evaluation of neuronal death in the cortex was carried out using Nissl staining, and the lactate content was also determined in rat brains. Results The average time-to-exhaustion in the rush-entry-into-altitude and the altitude inhibitor injection groups were (61.00±6.55) min and (71.25±9.59) min, respectively, which was significantly lower than that in the normal exercise (124.75±9.36) min and the 2-week-altitude acclimatization groups (100.25±9.74) min (P<0.05). Western blotting showed that, compared with the control group, the expression of MCT2 in the motor cortex in the 2-week-altitude acclimatization and the altitude inhibitor injection groups increased significantly by 120.6% and 164.4% (P<0.05), respectively; the expression of MCT4 in the two groups increased significantly by 174.6% and 168.8% (P<0.05). The results of western blotting were confirmed by the results of immunohistochemistry. In the high-altitude environment, the average lactate content in rat brains was significantly higher than that in the normal exercise group (0.175±0.021) mmol/g, P<0.05]. Neuropathological evaluation showed that the average neuronal density [neurons per high power field (HPF)] in the motor cortex in the rush-entry-into-altitude and the altitude inhibitor injection groups were (46.75±8.65) cells/HPF and (63.50±7.65) cells/HPF, respectively, which were significantly lower than that in the control group [(135.88±8.59) cells/HPF](P<0.05). Differences between the 2-week-altitude acclimatization [(121.75±16.00) cells/HPF] and the control groups were not statistically significant (P > 0.05). Conclusion The adaptability of the body to exercise fatigue after altitude acclimatization is correlated with changes in the expression of MCT2 and MCT4 in the brain, which can be used as targets for medical intervention for exercise-induced fatigue.

Key words: High altitude, Hypoxia, Exercise-induced fatigue, Monocarboxylate transporters, Lactate, Cerebral cortex, Rats

CLC Number:

G804.7

Chen GAO, Chunling FAN, Yurong LI, Wenjuan PEI, Caiping GUAN. Changes in Expression of Monocarboxylate Transporters in the Rat Cerebral Cortex after Exercise-induced Fatigue Under Simulated High-altitude Hypoxia and its Significance[J]. Laboratory Animal and Comparative Medicine, 2022, 42(5): 384-392.

Figures/Tables 6

Table 1 Average time–to–exhaustion in rats under exercise-induced fatigue conditions

分组 Group	平均运动力竭时间 Average exhaustion time /min
常规运动组 NE group	124.75±9.36^#△
急进高原组 REIA group	61.00±6.55^*
高原习服3 d组 3 d AA group	66.38±4.72^*
高原习服1周组 1 week AA group	73.13±7.02^*
高原习服2周组 2 weeks AA group	100.25±9.74^#△
高原抑制剂组 MTI group	71.25±9.59^*

Figure 1 Western blotting analysis of MCT2 and MCT4 expressions in the cerebral motor cortex of rats in each groupNote：CG: Control group； NE group: Normal exercise group； REIA group: Rush-entry-into-altitude group； 3 d AA group: 3-day-altitude acclimatization group； 1 week AA group: 1-week-altitude acclimatization group； 2 weeks AA group: 2-week-altitude acclimatization group； MTI group: Monocarboxylate transporter inhibitor group. *P＜0.05， versus CG group for MCT2 quantitative analysis; #P<0.05， versus CG group for MCT4 quantitative analysis, ANOVA with post hoc Bonferroni correction. n=3 for each group.

Figure 2 Immunohistochemical detection of MCT2 (A) and MCT4 (B) in the cerebral motor cortex of rats in each group (DAB staining, ×400)Note： A, MCT2 expression of neurons in the cerebral motor cortex of rats; B, MCT4 expression in astrocytes in the cerebral motor cortex of rats. a and a’, control group; b and b’, normal exercise group; c and c’, rush-entry-into-altitude group; d and d’, 3-day-altitude acclimatization group; e and e’, 1-week-altitude acclimatization group; f and f’, 2-week-altitude acclimatization group; g and g’, mono-carboxylate transporter inhibitor group. Scale bar = 25 μm.

Table 2 Histological grade and average neuronal density in the cerebral motor cortex of rats under exercise-induced fatigue conditions

分组 Group	神经元组织学分级 Neuronal histological grade (count)				平均神经元密度值 Average neuronal density/（cells·HPF^-1）
分组 Group	0级 0 grade	Ⅰ级 Ⅰ grade	Ⅱ级 Ⅱ grade	Ⅲ级 Ⅲ grade	平均神经元密度值 Average neuronal density/（cells·HPF^-1）
对照组 CG	3	0	0	0	135.88±8.59
常规运动组 NE group	2	1	0	0	123.88±6.71
急进高原组 REIA group	0	0	2	1	46.75±8.65^*
高原习服3 d组 3 d AA group	0	0	3	0	54.13±11.33^*
高原习服1周组 1 week AA group	0	2	1	0	119.50±6.99^*
高原习服2周组 2 weeks AA group	0	3	0	0	121.75±16.00
高原抑制剂组 MTI group	0	1	2	0	63.50±7.65^*

Figure 3 Nissl staining in the cerebral motor cortex of rats under exercise-induced fatigue conditions (×200，local enlarged image×400 )Note：a, control group; b, normal exercise group; c, rush-entry-into-altitude group; d, 3-day-altitude acclimatization group; e, 1-week-altitude acclimatization group; f, 2-week-altitude acclimatization group; g, monocarboxylate transporter inhibitor group. Scale bar = 50 μm.

Table 3 Average brain lactate content in rats under exercise-induced fatigue conditions

分组 Group	脑组织乳酸含量 Average brain lactate content/(mmol·g^-1)
对照组 CG	0.163±0.011^#△
常规运动组 NE group	0.175±0.021^#△
急进高原组 REIA group	0.239±0.017^*△
高原习服3 d组 3 d AA group	0.247±0.012^*△
高原习服1周组 1 week AA group	0.397±0.017^*#△
高原习服2周组 2 weeks AA group	0.412±0.024^*#△
高原抑制剂组 MTI group	0.537±0.011^*#

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