TRPV4 plays an important role in rat prefrontal cortex changes induced by acute hypoxic exercise

OBJECTIVE: This study aims to investigate the effects of TRPV4 on acute hypoxic exercise-induced central fatigue, in order to explore the mechanism in central for exercise capacity decline of athletes in the early stage of altitude training. METHODS: 120 male Wistar rats were randomly divided into 12 groups: 4 normoxia groups (quiet group, 5-level group, 8-level group, exhausted group), 4 groups at simulated 2500 m altitude (grouping as before), 4 groups at simulated 4500 m altitude (grouping as before), 10 in each group. With incremental load movement, materials were drawn corresponding to the load. Intracellular calcium ion concentration was measured by HE staining, enzyme-linked immunosorbent assay, immunohistochemistry, RT-qPCR, Fluo-4/AM and Fura-2/AM fluorescence staining. RESULTS: (1) Hypoxic 2–5 groups showed obvious venous congestion, with symptoms similar to normoxia-8 group; Hypoxic 2–8 groups showed meningeal loosening edema, infra-meningeal venous congestion, with symptoms similar to normoxia-exhausted group and hypoxic 1-exhaused group. (2) For 5,6-EET, regardless of normoxic or hypoxic environment, significant or very significant differences existed between each exercise load group (normoxic − 5 level 20.58 ± 0.66 pg/mL, normoxic − 8 level 23.15 ± 0.46 pg/mL, normoxic - exhausted 26.66 ± 0.71 pg/mL; hypoxic1-5 level 21.72 ± 0.43 pg/mL, hypoxic1-8 level 24.73 ± 0.69 pg/mL, hypoxic 1-exhausted 28.68 ± 0.48 pg/mL; hypoxic2-5 level 22.75 ± 0.20 pg/mL, hypoxic2-8 level 25.62 ± 0.39 pg/mL, hypoxic 2-exhausted 31.03 ± 0.41 pg/mL) and quiet group in the same environment(normoxic-quiet 18.12 ± 0.65 pg/mL, hypoxic 1-quiet 19.94 ± 0.43 pg/mL, hypoxic 2-quiet 21.72 ± 0.50 pg/mL). The 5,6-EET level was significantly or extremely significantly increased in hypoxic 1 environment and hypoxic 2 environment compared with normoxic environment under the same load. (3) With the increase of exercise load, expression of TRPV4 in the rat prefrontal cortex was significantly increased; hypoxic exercise groups showed significantly higher TRPV4 expression than the normoxic group. (4) Calcium ion concentration results showed that in the three environments, 8 level group (normoxic-8 190.93 ± 6.11 nmol/L, hypoxic1-8 208.92 ± 6.20 nmol/L, hypoxic2-8 219.13 ± 4.57 nmol/L) showed very significant higher concentration compared to quiet state in the same environment (normoxic-quiet 107.11 ± 0.49 nmol/L, hypoxic 1-quiet 128.48 ± 1.51 nmol/L, hypoxic 2-quiet 171.71 ± 0.84 nmol/L), and the exhausted group in the same environment (normoxic-exhausted 172.51 ± 3.30 nmol/L, hypoxic 1-exhausted 164.54 ± 6.01 nmol/L, hypoxic 2-exhausted 154.52 ± 1.80 nmol/L) had significant lower concentration than 8-level group; hypoxic2-8 had significant higher concentration than normoxic-8. CONCLUSION: Acute hypoxic exercise increases the expression of TRPV4 channel in the prefrontal cortex of the brain. For a lower ambient oxygen concentration, expression of TRPV4 channel is higher, suggesting that TRPV4 channel may be one important mechanism involved in calcium overload in acute hypoxic exercise.