Abstract
Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotropic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus Wild Type (Val/Val)) influenced the ability of voluntary running to increase neurogenesis and cognition in mice. C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touch screen-based technology to evaluate cognitive flexibility. BDNF Val/Val mice outperformed BDNF Met/Met mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT results in improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.
Highlights
BDNF Val/Val mice performed better than BDNF Met/Met mice in middle-age
Aerobic training (AT) increased cognitive performance in BDNF Met/Met mice
AT increased neurogenesis in middle-aged BDNF Val/Val mice only
Female BDNF Val/Val mice had better cognitive flexibility than males regardless of AT
AT increased more mature new neurons in middle-aged female mice
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# denotes co-first author