## 4 Discussion  
Exercise affects the sensitivity of stress-related hormones; modulates neurotransmitters, such as serotonin and dopamine; produces mood-enhancing effects, such as reduced depressive behavior; and restores normal levels of endocrine system responses, nerve growth factors, and neural stem cells through feedback regulation of the HPA axis [15; 16; 27; 28]. Intense exercise enhances protective mechanisms against depression by increasing neurite outgrowth, neuronal proliferation, and survival in response to acute stress and certain levels of CORT treatment [29; 30; 31]. Therefore, the present study aimed to investigate the neuroprotective effects of different exercise intensities, including HIIT, via brain neurogenesis in an animal model of RST-induced depressive behavioral disorders. Recently, many researchers have attempted to induce depressive disorders by applying various forms of stress, such as RST, which restricts movement for 2 h a day for 14 d and promotes modifications in the brain's neural networks; such phenomena cause behav  
Figure 5: The effects of treadmill exercise on 4 HNE and MDA in the hippocampus of mice with restraint stress-induced depressive disorder. (**A**) Representative western blot image of 4 HNE signaling (\(n\) = seven per group). (**B**) Quantification of 4 HNE levels. (**C**) MDA levels based on ELISA analysis (\(n\) = twelve per group). Bonferroni post hoc test after ANOVA. Values are the mean \(\pm\) SD. * \(p\) < 0.05 vs. CON; # \(p\) < 0.05 vs. RST. Figure 6: The effects of treadmill exercise on serotonin and corticosterone in the serum of mice with restraint stress-induced depressive disorder. (**A**,**B**) Serotonin and corticosterone levels based on ELISA analysis (\(n\) = twelve per group). [PERSON] post hoc test after ANOVA. Values are the mean \(\pm\) SD. * \(p\) < 0.05 vs. CON; # \(p\) < 0.05 vs. RST. ioral hopelessness and anhedonia, which is reported to be the closest to depression-like behavior [32; 33; 34]. In the present study, FST and SPT were conducted to analyze the effects of different exercise intensities on anxiety and depression-like behaviors caused by RST. NORT was performed to analyze the learning and memory abilities of the experimental animals, and their aerobic capacity was determined according to the exercise intensity. In all behavioral tests, the RST group showed increased anxiety and depression-like behaviors, decreased cognitive function, and decreased aerobic capacity. These results suggest that 14 days of RST for 2 h daily is physiologically appropriate to induce anxiety and depression-like behaviors. Two weeks of treadmill exercise combined with RST produced positive results in all tests, with the HIIT group showing more positive results than the moderate- and high-intensity exercise groups. This is consistent with the findings of [PERSON] [35] and [PERSON] [36]. Exercise is thought to improve behavioral functioning not only because of its antidepressant effects but also because it improves the metabolic capacity of the cardiorespiratory system and the functioning of the CNS [20; 21]. Various neuoplastic pathways play important roles in the pathophysiology and treatment of depression [37; 38; 39]. Among the various neuoplastic pathways in depression, attention has been focused on the BDNF, TrkB, and CREB pathways [38; 40]. Specifically, BDNF is involved in cognitive enhancement by improving brain plasticity and enhancing learning and memory functions in the hippocampus [41]. Increased BDNF synthesis in the brain is associated with increased BDNF signaling, resulting in improved mood, cognitive function, and memory [42]. In the present study, the BDNF, CREB1, and TrkB levels were reduced in the RST group. Stress reduces the expression of BDNF in the hippocampus and prefrontal cortex, which consequently reduces TrkB signaling possibly via the cAMP-CREB1 signaling pathway [43; 44].