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Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice

Dannia Islas-Preciado, View ORCID ProfileTallinn F.L. Splinter, Muna Ibrahim, Natasha Black, Sarah Wong, Teresa Liu-Ambrose, Cindy K Barha, View ORCID ProfileLiisa A.M. Galea
doi: https://doi.org/10.1101/2022.07.29.502070
Dannia Islas-Preciado
1Department of Psychology
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Tallinn F.L. Splinter
2Department of Biology
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  • ORCID record for Tallinn F.L. Splinter
Muna Ibrahim
1Department of Psychology
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Natasha Black
1Department of Psychology
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Sarah Wong
1Department of Psychology
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Teresa Liu-Ambrose
3Department of Physical Therapy
4Dajavad Mowifaghian Centre for Brain Health
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Cindy K Barha
3Department of Physical Therapy
4Dajavad Mowifaghian Centre for Brain Health
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  • For correspondence: liisa.galea@ubc.ca
Liisa A.M. Galea
1Department of Psychology
4Dajavad Mowifaghian Centre for Brain Health
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  • ORCID record for Liisa A.M. Galea
  • For correspondence: liisa.galea@ubc.ca
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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

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 31, 2022.
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Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice
Dannia Islas-Preciado, Tallinn F.L. Splinter, Muna Ibrahim, Natasha Black, Sarah Wong, Teresa Liu-Ambrose, Cindy K Barha, Liisa A.M. Galea
bioRxiv 2022.07.29.502070; doi: https://doi.org/10.1101/2022.07.29.502070
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Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice
Dannia Islas-Preciado, Tallinn F.L. Splinter, Muna Ibrahim, Natasha Black, Sarah Wong, Teresa Liu-Ambrose, Cindy K Barha, Liisa A.M. Galea
bioRxiv 2022.07.29.502070; doi: https://doi.org/10.1101/2022.07.29.502070

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