Effects of sequential exposure to physical exercise and cognitive training on hippocampal neurogenesis in mice

AIMS: Physical exercise and cognitive training hippocampal dependent tasks are known to enhance adult hippocampal neurogenesis (AHN). Here we aimed to evaluate the effect of either a moderate-intensity exercise protocol, a working memory task and the combination of both treatments on mice AHN. METHODS: Adult male C57BL6/J mice (N=34) were submitted to a scheduled treadmill exercise protocol for 12 days (EX-groups) or remained at home cage (SED-groups). 24 hours later, animals either were perfused or trained in a spatial learning task in the Water Maze (WM groups) for 8 days while control groups remained at home cage (CAGE groups). Bromodeoxyuridine (BrdU) was injected at the beginning of every experimental procedure to label hippocampal cells that proliferated during the initial exercise sessions. RESULTS: Mice submitted to scheduled exercise showed an increased number of BrdU+ and PCNA+ dentate granule cells (DGCs) in the short but not in the long-term when compared to sedentary groups. Conversely, training in the WM solely reduced the amount of BrdU+ and PCNA+ DGCs compared to CAGE group. However, animals submitted to scheduled exercise and WM training showed increased proliferation/survival of DGCs in the long-term compared to all other groups. CONCLUSIONS: Our data suggests that the combination of moderate-intensity exercise with spatial training has a powerful neurogenic effect in the DG, being a valuable non-pharmacological strategy for the treatment of neurodegenerative diseases associated with impaired AHN. Funding: PSI2017-82604; PRE2018-085673; FPU20/00908; 08-2021-AREA3; B1-2020_06; Posdoc_21_00222; Posdoctoral_a32. I Plan Propio de Investigación, Transferencia y Divulgación Científica de la Universidad de Málaga.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sequential treadmill exercise and cognitive training synergistically increase adult hippocampal neurogenesis in mice

Combining physical and cognitive training has been suggested to promote further benefits on brain and cognition, which could include synergistic improvement of hippocampal neuroplasticity. In this paper, we investigated whether treadmill exercise followed by a working memory training in the water maze increase adult hippocampal neurogenesis to a greater extent than either treatment alone. Our results revealed that ten days of scheduled running enhance cell proliferation/survival in the short-term as well as performance in the water maze. Moreover, exercised mice that received working memory training displayed more surviving dentate granule cells compared to those untreated or subjected to only one of the treatments. According to these findings, we suggest that combining physical and cognitive stimulation yield synergic effects on adult hippocampal neurogenesis by extending the pool of newly-born cells and subsequently favouring their survival. Future research could take advantage from this non-invasive, multimodal approach to achieve substantial and longer-lasting enhancement in adult hippocampal neurogenesis, which might be relevant for improving cognition in healthy or neurologically impaired conditions.This study received financial support from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación, AEI), which was cofounded by the European Regional Development Fund (AEI/FEDER, UE; PSI2017-82604R to L.J.S.); by the Spanish Ministry of Science and Innovation (PID2020-113806RB-I00 to L.J.S); by the Biomedical Research Institute of Málaga (IBIMA; 08-2021-AREA3 to D.L.G.M) and by the University of Málaga (B1-2020_06 to D.L.G-M). Funding for Open Access charge: Universidad de Málaga/CBU