Does resistance exercise exert a role in hippocampal neurogenesis?

We read with great interest the paper by Nokia and collaborators (2016) that demonstrates the effects of different types of exercise on adult hippocampal neurogenesis (AHN). We applaud them for pursuing this subject, but we are also interested in addressing some issues concerning this research. In their study, rats selectively bred for low (LRT) and high (HRT) response to aerobic exercise training were subjected to 6–8 weeks of resistance exercise (RES), voluntary wheel running (WR), high-intensity interval training (HIT), and endurance training (END). Consistent with previous studies, the number of adult-born hippocampal neurons was increased in rats subjected to WR and END. However, AHN was not significantly altered in animals from the HIT and RES groups. Considering that moderate, but not intense, exercise increases the number of new neurons (BrdU+/NeuN+ cells) (Inoue et al. 2015), Nokia et al. (2016) suggested that the lack of significant changes in AHN and HIT groups might be attributed to the high intensity and short volume of exercise performed in each session. We have recently reported an increase in hippocampal cell proliferation after 4 weeks of resistance exercise (Novaes Gomes et al. 2014). Nokia and co-workers raised some hypotheses that could explain the discrepancies between our and their study. They suggested that the effects of resistance training can be transient, with increasing hippocampal cell proliferation only in early stages of training. Although both studies performed the similar experimental model of resistance training, it is important to point out that some different parameters were used for the resistance exercise in these studies. While in the study of Novaes Gomes et al. (2014) the rats were submitted to 4 weeks (5 days per week) of resistance training with sessions composed of eight climbs (50–100% of the maximum load capacity assessed once a week) with 60 s rest intervals between them. The rats of the Nokia et al. (2016) study were subjected to 6–8 weeks (3 days per week) of resistance training where each session was constituted of nine climbs (50–90% of the previous maximum load capacity plus 30 g until they reach a new maximal load) with 90 s rest intervals between them. Interestingly, several studies conducted in humans (for review see Spiering et al. 2008) have demonstrated that the manipulation of resistance exercise variables (i.e. load, volume and rest intervals between sets) can profoundly affect the adaptive response to this type of exercise. Therefore, we cannot exclude the possibility that the different resistance exercise protocols performed between these two studies can be, at least partially, responsible for the discrepancies regarding the AHN. As pointed out by Nokia et al. (2016), the absence of changes in AHN after the resistance training may be related to the fact that expression of BDNF, a neurotrophic factor with an essential role in the regulation of AHN, was not altered in the hippocampus of rats subjected to 8 weeks of resistance training (Cassilhas et al. 2012). In the study of Cassilhas and collaborators (2012), resistance-trained rats presented an increase of peripheral and hippocampal IGF-1 levels with concomitant activation of its receptor IGF-1R and downstream targets. This suggests that this neurotrophic factor, which also has a critical role on AHN, is more sensitive to this type of exercise. Therefore, as a result of the points raised above, we believe that the use of different resistance exercise variables in the studies of Nokia et al. (2016) and Novaes Gomes et al. (2014) may have contributed, at least partially, to the discrepancies of the findings. We would like to express our congratulations to Nokia and colleagues for their interesting paper that adds to our understanding of the neuroplasticity induced by different types of exercise. Further studies should be conducted to address how the manipulation of resistance exercise parameters can affect AHN as well as other morphological, molecular and behavioural changes induced by this type of exercise.