Brain derived neurotrophic factor (BDNF, 14-kDa) is a member of the neurotrophic factor family [1] such as nerve growth factor, neurotrophin-3, neurotrophin-4/5, and neurotrophin-6 and a protein encoded by the BDNF gene [2]. It is known that BDNF plays a major role in controlling structural and functional plasticity of the brain and improving learning and memory functions. Arbitrary participation on exercise may, therefore, increase mRNA in BDNF and protein in hippocampus and other areas of the brain [3].

A recent study mentioned that increase in mRNA in BDNF and protein followed by skeletal muscle contraction is caused by histone deacetylease suppression. This rational came from previous animal studies showing expression of mRNA in BDNF during the suppression of histone deacetylease [4]. Likewise, mRNA in BDNFexpression and protein during skeletal muscle contraction has been expected to provide a positive effect on improvement of energy homeostasis and circulation of BDNF. Moreover, it has been asserted that mRNA of BDNF expression and protein during skeletal muscle contraction is linked with metabolic disorders such as obesity and diabetes [5-8]_ENREF_5].

It has been reported that mid-aged Korean women have a noticeable change of mood swing induced by low level of exercise and a higher risk of metabolic disorders due to a decrease in fitness level [9,10]. Besides, it has been also reported that mid-aged women with depression have decreased level of BDNF [11]; however, information on exercise method for increasing BDNF is limited. Also, as decision on exercise duration and intensity is answered personally by participants, it is difficult in conducting aerobic exercise and skeletal muscle training while keeping the level of exercise duration and intensity consistent for all individuals. Also, it is hard to determine which of the factors, aerobic exercise and skeletal muscle training, were responsible for the effect on BDNF. Although acute aerobic exercise increased the level of serum BDNF [12,13], there are not enough studies focusing on long term exercise effect related to BDNF change and cardiometabolic risk factors. Moreover, most previous studies reported that serum BDNF level has not been significantly increased from skeletal muscle training [14-16]. Therefore, combined exercise of aerobic and resistance exercise may have a positive effect on decreasing metabolic risks and increasing level of BDNF level in mid-aged women.

Major findings of this study are as follows; 1) there was a significant difference in BMI and percent body fat after 24-week exercise intervention, which showed no significant difference in AEG and CEG compared to CG, 2) after 24-week exercise intervention, AEG showed a significant increase in VO₂max, HDL-C, and serum BDNF level compared to CG, 3) there was a significant increase in serum BDNF of CEG and a significant decrease in TG and TC/HDL-C of CEG, and 4) there was no significant difference between AEG and CEG.

Generally, it has been well known that regular training induces a positive effect on body composition changes, decreases in blood cholesterols such as TG, TC, and LDL-C [20], an increase in HDL-C [21], increases in insulin sensitivity [22]. Especially, it has been reported that percent body fat and blood cholesterols have a negative relationship with insulin sensitivity and there existed a positive relationship in HDL-C and aerobic capacity [22]. Although it was observed that regular aerobic exercise induced decreased percent body fat and significantly increased HDL-C in mid-aged women, combined exercise showed significant changes in percent body fat, muscular strength, TG, and TC/HDL-C and higher changes in TC, TG/HDL-C, glucose, insulin, and HOMA IR compared to aerobic exercise without statistical significance. Thus, it seems that combined exercise have a positive effect on improving metabolic risk factors in mid-aged women as CEG had significantly different variables compared to AEG (percent fat) and CG (BMI, percent fat, peak torque flexion and extension, TG, TC/HDL-C) and there was no noticeable metabolic risk factors in AEG and CEG. Similar to this study, Park et al. [23] reported that combined exercise showed a more positive effect on improving VO₂max, percent body fat, blood cholesterols, and lipoproteins than aerobic exercise after 24-week intervention in mid-aged obesity women. Our conducted study used similar muscular strength exercise frequency of CEG as that of Park et al. (2003)’s study however, our study used 30% lower exercise intensity (1RM, 30-40%) compared to (1RM, 60-70%) and this may be reflected in the results.

For healthy adults, it is recommended that exercise intensity of aerobic and resistant exercise to be divided into moderate exercise ≥3-5 days per week and high intensity exercise ≥ = 2-3 days per week [24]. All participants, therefore, were supervised by this guideline. The present study conducted a 60-minute moderate level of combined exercise for 4 days per week for 6 months in mid-aged women, andVO₂max induced by muscle hypertrophy and increased muscular strength is expected improve. However, results showed that VO₂max of AEG was significantly improved compared to CG while changes in VO₂max of AEG were greater than that of CEG. While the cause of such result is unclear, having conducting both aerobic and resistance exercise on the same day may have affected restricted muscle hypertrophy and muscular improvement [25] along with lower level of muscular strength exercise intensity(1 set, 1 RM: 30-40%). Eventually, it seems that this might cause lower improvement in VO₂max of CEG compared to AEG. Comparing muscular strength of CEG and CG, we also found that there was a greater differences in CEG and CG than AEG and this in agreement with the previous study [25]. They commented that one-time exercise and chronic exercise training caused muscular strength induced by improved muscle hypertrophy.

Several previous studies proved that acute aerobic exercise increased serum BDNF level [26-30] and similarly, we have previously reported [13] an improved serum BDNF level after acute aerobic exercise intervention. Therefore, it can be easily considered that long term aerobic exercise can cause increased serum BDNF level. Erickson et al. [31] and Ruscheweyh et al. [32] reported that increased serum BDNF level after 6 and 12-month aerobic exercise intervention for older adults corresponds with our study results. On the other hand, Griffin et al. [27] found that there was no change in serum BDNF level after 3-5 week aerobic exercise intervention for young male adults, which contradicts results from both Erickson et al. [31], Ruscheweyh et al. [32], and our current results. Although exercise intensity of our study was similar to that of Griffin et al.’s [27] (60% VO₂max), Erickson et al. [31] and Ruscheweyh et al. [32] (60-80% VO₂max), young male adults participating in aerobic exercise caused higher changes in BDNF revelation of muscle [33], adipose cells [34], other peripheral nerves, and brain tissue [1] compared to mid-aged women and older adults. Therefore, the results from the three studies seem to be inconsistent. Also, no difference in aerobic exercise and combined exercise caused any significant serum BDNF concentration and this may be due to lower combined exercise intensity (1 set, 1 RM: 30-40%). Huang et al. [35] expected that increased BDNF level induced by acute exercise is relatedto exercise intensity. According to this expectation, we may conclude that combined exercise might not induce more significantly increased serum BDNF concentration than aerobic exercise.

This study had the following limitations; 1) dietary intake and nutritional supplementation of all participants was not considered, 2) cognitive function effects on serum BDNF changes during training period was not regarded, 3) abnormal menstrual status of each participant was not considered as one of confounding factors on BDNF changes in mid-aged women, and 4) BDNF changes and circulating BDNF level (serum, plasma, platelet) at baseline, after treatment, and recovery phase was not calculated.

Aerobic exercise and combined exercise resulted in a significant decrease in body fat of mid-aged women during the 24 weeks. Comparing baseline change for the 24 weeks, VO₂max and HDL-Cwere significantly increased for AEG and CG. Significant levels of TG and TC/HDL-C was decreased in CEG during the 24 week period. Moreover, serum BDNF concentration for both AEG and CEG was significantly increased compared to CG. However, there was no significant difference between the groups. Although there was no difference in serum BDNF level between AEG and CEG, we confirmed that CEG may evoke a positive change in BDNF increase of mid-aged women.