Effects Of Aerobic Exercise On PGC-1α,NRF-1 And TFAM In Cerebral Cortex Of Depression Model Rats

Objective: Depression has become a global disease that damages brain function due to long-term mental disorders caused by stress.Studies have shown that aerobic exercise can reduce the incidence of depression,and also improve the ability of mitochondrial biosynthesis.The mitochondrial energy metabolism disorder mechanism of depression is still unclear.In this study,chronic unpredictable mild stress(CUMS)was used to induce depression in SD rats.Aerobic exercise was performed at different periods to investigate the effects of aerobic exercise on the cerebral cortex PGC-1α,NRF-1 and TFAM expression,in order to explore the role of exercise from the perspective of mitochondrial biosynthetic capacity and the mechanism of depression in rats.To provide a biological theoretical basis for improving depression from the perspective of molecular biology.Methods: Forty eight 3-month-old SPF-grade SD male rats were selected as the research object,and the principle of random grouping was adopted as follows:(1)The blank control group(group C)was only given natural feeding for eight weeks;(2)CUMS model group(group M),the CUMS model was established in the first four weeks,and only natural feeding was performed for the next four weeks,for a total of eight weeks;(3)The CUMS model exercise group(group E1),the CUMS model was established in the first four weeks and aerobic exercise was simultaneously performed,and the natural feeding was performed in the last four weeks,for a total of eight Week;(4)Post-depression exercise group(group E2),the CUMS model was established in the first four weeks,and aerobic exercise was performed in the last four weeks,for a total of eight weeks.During the experiment,the status of the rats was observed in time,and their weight were recorded in time.The sugar-water preference test,the open field test and Elisa test were performed according to the experimental progress to verify whether the CUMS model was successfully modeled.After eight weeks,the specimens of rats were collected,we used Western Blotting and Real-Time PCR to detect the expression,the protein content of PGC-1α,TFAM and the gene expression of PGC-1α,NRF-1,TFAM in cerebral cortex of each group,to study the effects of aerobic exercise on PGC-1α,NRF-1,TFAM during mitochondrial biosynthesis in depressive ratsResults:(1)The results of establishing CUMS model:(1)General condition: Rats in group C showed stable performance,with smooth and elastic hair,and maintained the same drinking water and diet;the water intake of group M rats showed a downward trend,and hair loss was serious;the daily condition of rats in E1 group tended to be stable;The condition of the E2 group was consistent with that of the M group in the first four weeks.After the exercise intervention,the water intake began to develop toward the normal state,and the basic situation remained unchanged.(2)Weight changes: Before modeling,the weights of rats in each group were relatively consistent.After modeling,the weights of rats in group M,E1 and E2 were lower than group C,and the difference was significant(P<0.05),Compared with the group E1 and group E2,the group M has no significant difference and remains basically the same.(3)Sugar-water preference test: After modeling,the sugar-water consumption ratios of rats in group M and group E2 were lower than group C,the difference was significant(P <0.01).The sugar-water consumption ratio of rats in group E1 was not significantly different from that in group C.(4)Open field test results: The activity,total distance,average speed,central area distance,and central area time of the group M were decreased.Compared with the other three groups,the activity and total distance of the group M were significantly different(P <0.01).The activity of the group E1 and E2 was lower than group C and the difference was significant(P <0.01),the central area distance and time of the group E1 and E2 were higher than those of the group C.(2)Results of in vitro experiments:(1)NE results detected by ELISA: The NE content in the whole brain of group M rats was lower than the other three groups,which was significantly lower than that of group C(P<0.01).(2)Western Blotting: The protein expression of PGC-1α and TFAM in the cortex of group M rats was significantly lower than the other three groups.The protein expression of PGC-1α and TFAM in the cortex of group M was significantly different from that of group C(P<0.01).The protein expression of PGC-1α and TFAM in the group E1 and E2 was higher than those in the group M,and the differences were significant(P<0.05).The protein expression levels of PGC-1α and TFAM in the group E1 was close to those in the group C and E2,and that was no significant difference.(3)Real-Time PCR: The expression of PGC-1α,NRF-1 and TFAM genes in the cortex of group M was significantly different from that of group C(P<0.01).The expression levels of PGC-1α,NRF-1,and TFAM genes in the group E1 and E2 was higher than those in the group M,and the difference between the group E1 and group M was significant(P<0.01).The expression levels of PGC-1α,NRF-1 and TFAM genes in rats in group E2 were lower than those in group E1,which was similar to that in group C.Conclusion:(1)Chronic unpredictable mild stress stimulation resulted in decreased activity,significantly reduced sugar-water consumption and depressive symptoms in rats;In the cerebral cortex of depressed rats,the content of PGC-1α was decreased,and the promoting effect of NRF-1 was weakened,resulting in the decrease of TFAM content,which affected the ability of mitochondrial biosynthesis and led to energy metabolism disorder.(2)Aerobic exercise can improve the activity of depressive rats,increase the sugar water consumption of depressive rats,increase the content of PGC-1α in the cerebral cortex of depressive rats,enhance the promotion of NRF-1,and then cause the increase of TFAM content,and improve the ability of mitochondrial biosynthesis of depressive rats.(3)With chronic unpredictable mild stress,the ability of mitochondrial biogenesis by exercise intervention during depression was higher than the ability of mitochondrial biogenesis during exercise intervention after stimulation.Early exercise intervention is beneficial to alleviate energy metabolism disorders and helps to improve depressive behavior.