Effects Of Hypoxic Training On Gdnf In The Cortex Of Obese Rats

Abstract

Glial cell-derived neurotrophic factor (GDNF) is an important indicator that represent the function of nervous system. Exercise and hypoxic environment both can reduce weight and improve nervous system function in obese rats. But the mechanism by which hypoxic training affects the nervous system is unclear. PURPOSE: To determine the potential mechanisms of hypoxic training on GDNF in the cortex of obese rats. METHODS: Forty SD obese rats were assigned into one of the following groups (n=10 each): normal oxygen control group (NC), normal oxygen training group (NT), hypoxic control group (HC) and hypoxic training group (HT). Rats were kept continuous exercise 1 hour per day, 6 days per week for 4 weeks on a rat treadmill at a speed of 25 m/min in normoxic conditions or 20 m/min in hypoxic conditions (13.6% O2). After 4 weeks, the expressions of GDNF in the cortex were detected by quantitative fluorescent PCR and Western blotting. The level of inflammatory cytokine interleukin 1β (IL-1β) and interleukin 6 (IL-6) in the cortex were measured by ELISA. The phosphorylation of ERK1/2 and JNK of cortex were detected by Western blotting. RESULTS: 1) The results of qPCR showed that the expression of GDNF in the cortex of HT were higher than NT and HC (2.75±0.69 vs. 1.66±0.88 and 1.06±0.45, p<0.05). 2) The results of Western blotting showed that the expression of GDNF in the cortex of HT were higher than NT and HC (489±23.58 vs. 337±46.22 and 387±36.98, p<0.05). 3) The results of phosphorylation of ERK1/2 and JNK showed that the ratio of ERK1/2 and JNK to β-actin integral optical density in the cortex showed no significant difference in all groups(p>0.05), while compared with NC, the ratio of p-ERK1/2 to ERK1/2 and p-JNK to JNK integral optical density in HC, NT and HT were significantly increased (P < 0.05, P < 0.05, P < 0.01). 4) The results of ELISA showed that IL-1β and IL-6 serum levels in HC, NT and HT were decreased compared with NC (19.28±1.41,19.99±1.26 and 17.8±1.5 vs. 27.15±2.27, p<0.01; 53.82±2.54,57.53±1.96 and 52.22±1.4 vs. 66.87±2.73, p<0.01). CONCLUSION: Hypoxic training can increase the expression of GDNF in the cortex of obese rats and improve the function of the central nervous system. Its mechanisms may relate to the activation of ERK1/2 and JNK signaling pathways and inhibit inflammatory cytokine IL-1β and IL-6 level in the cortex.