Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model

“…Our data are seemingly in contradiction with previous studies reporting that enhancing adult neurogenesis is associated with improved cognitive functions in AD mice ( Choi et al., 2018 ; Fiorentini et al., 2010 ; Richetin et al., 2015 ; Wang et al., 2010 ). However, we believe that the effects of deleting abnormal new neurons and enhancing healthy new neurons on AD pathology are not mutually exclusive: (1) enhancing adult neurogenesis plus exercise or brain-derived neurotrophic factor (BDNF) but not enhancing adult neurogenesis alone improves cognitive functions in AD mice ( Choi et al., 2018 ). Both exercise and BDNF are known to improve the hippocampal microenvironment, which supports the generation and survival of healthy newborn neurons ( Scharfman et al., 2005 ; van Praag et al., 1999 ); (2) restoring dendritic spines without increasing the overall number of new neurons after overexpression of NeuroD1 in aNSCs rescues spatial memory in AD mice ( Richetin et al., 2015 ); (3) as shown in our current study, ablating aNSCs restores the normal synaptic transmission in the GCs of AD mice, suggesting that abnormal new neurons may contribute to the aberrant synaptic transmission that is associated with the dysfunction of hippocampal neural circuits and hippocampus-dependent cognition ( Palop et al., 2007 ); (4) similar to our results in AD mice, reducing aberrant newborn neurons by ablation of aNSCs improves hippocampus-dependent memory in an epilepsy model ( Cho et al., 2015 ).…”