RT Journal Article
SR Electronic
T1 Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.29.502070
DO 10.1101/2022.07.29.502070
A1 Dannia Islas-Preciado
A1 Tallinn F.L. Splinter
A1 Muna Ibrahim
A1 Natasha Black
A1 Sarah Wong
A1 Teresa Liu-Ambrose
A1 Cindy K Barha
A1 Liisa A.M. Galea
YR 2022
UL http://biorxiv.org/content/early/2022/07/31/2022.07.29.502070.abstract
AB 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.HighlightsBDNF Val/Val mice performed better than BDNF Met/Met mice in middle-ageAerobic training (AT) increased cognitive performance in BDNF Met/Met miceAT increased neurogenesis in middle-aged BDNF Val/Val mice onlyFemale BDNF Val/Val mice had better cognitive flexibility than males regardless of ATAT increased more mature new neurons in middle-aged female miceCompeting Interest StatementThe authors have declared no competing interest.