1. Sex and BDNF Val66Met polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice.
- Author
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Islas-Preciado, Dannia, Splinter, Tallinn F.L., Ibrahim, Muna, Black, Natasha, Wong, Sarah, Lieblich, Stephanie E., Liu-Ambrose, Teresa, Barha, Cindy K., and Galea, Liisa A.M.
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DEVELOPMENTAL neurobiology , *BRAIN-derived neurotrophic factor , *SINGLE nucleotide polymorphisms , *AEROBIC exercises , *VISUAL discrimination , *NEUROGENESIS , *TOUCH screens - Abstract
Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic 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 enhance cognition and hippocampal neurogenesis in mice. Middle-aged 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 touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val 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 performance in 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 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. • BDNF Met/Met mice performed worse than BDNF Val/Val 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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