Shaping hippocampal neurogenesis: exercising the brain with cannabinoids

Adult neural stem/progenitor cells (NSPC) are present in specialized niches of the mammalian brain and their proliferative and differentiative potential is modulated by a myriad of factors. Recent evidence sheds light on the interaction between cannabinoids and neurotrophic factors underlying a major regulative force of adult hippocampal neurogenesis, with important effects upon cognitive plasticity and mood flexibility. Herein, we aimed at evaluating the actions of cannabinoid type 2 receptor (CB2R) together with exercise upon hippocampal neurogenesis and whether this has significant behavioral implications. Our data suggests a participation of CB2Rs in fine-tuning the actions of physical exercise upon adult hippocampal neurogenesis. Specifically, CB2R ligands as well as exercise-regulated neurotrophic factors promote an acceleration in the differentiation of progenitor cells accompanied by an increase in the number of mature neurons in vitro. Moreover, preliminary results show that CB2Rs play an impactful role in controlling cognitive and depressive-like behavior. This is particularly important because brain physiology and mental health are known to be greatly affected by physical exercise, with adult neurogenesis playing a significant role in this process. Ultimately, this work will contribute to unravel the mechanisms behind the actions of cannabinoids and exercise in the brain and to develop strategies utilizing CB2Rs and physical exercise to boost neural stem cell capacity and treat several brain disorders. Acknowledgements: Supported by Fundação para a Ciência e a Tecnologia (FCT), projects SFRH/BD/129710/2017 and IF/01227/2015. No potential conflict of interest.