Voluntary running rescues the defective hippocampal neurogenesis and behaviour observed in lipocalin 2-null mice

The continuous generation of new neurons in the adult mammalian hippocampus is a form of neural plasticity that modulates learning and memory functions, and also emotion (anxiety and depression). Among the factors known to modulate adult hippocampal neurogenesis and brain function, lipocalin-2 (LCN2) was recently described as a key regulator of neural stem cells (NSCs) proliferation and commitment, with impact on several dimensions of behaviour. Herein, we evaluated whether voluntary running, a well-known regulator of cell genesis, rescue the deficient adult hippocampal neurogenesis observed in mice lacking LCN2. We observed that running, by counteracting oxidative stress in NSCs, reverses LCN2-null mice defective hippocampal neurogenesis, as it promotes NSCs cell cycle progression and maturation, resulting in a partial reduction in anxiety and improved contextual behaviour. Together, these findings demonstrate that running is a positive modulator of adult hippocampal neurogenesis and behaviour in mice lacking LCN2, by impacting on the antioxidant kinetics of NSCs.
Ana Catarina Ferreira is recipient of PhD fellowship from the Foundation for Science and Technology (FCT, Portugal)/FEDER. Fernanda Marques is an assistant researcher IF/00231/2013 of the Foundation for Science and Technology (FCT, Portugal). Tis work was supported by Foundation for Science and Technology (FCT) and COMPETE through the project EXPL/NEU-OSD/2196/2013 (to Marques F) and by the Bial Foundation through Grant 217/12 (to Sousa JC). Te work at ICVS/3B’s has been developed under the scope of the project NORTE01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and funded by FEDER funds through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038.