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

  • Horm Behav. 2023 Feb:148:105297. doi: 10.1016/j.yhbeh.2022.105297.
Dannia Islas-Preciado  1 ,  Tallinn F L Splinter  2 ,  Muna Ibrahim  3 ,  Natasha Black  3 ,  Sarah Wong  3 ,  Stephanie E Lieblich  3 ,  Teresa Liu-Ambrose  4 ,  Cindy K Barha  5 ,  Liisa A M Galea  6
Affiliations
  • 1. Department of Psychology, University of British Columbia, Canada; Dajavad Mowifaghian Centre for Brain Health, University of British Columbia, Canada; Lab de Neuropsicofarmacología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México 14370, México.
  • 2. Department of Biology, University of British Columbia, Canada.
  • 3. Department of Psychology, University of British Columbia, Canada.
  • 4. Department of Physical Therapy, University of British Columbia, Canada; Dajavad Mowifaghian Centre for Brain Health, University of British Columbia, Canada.
  • 5. Department of Physical Therapy, University of British Columbia, Canada; Dajavad Mowifaghian Centre for Brain Health, University of British Columbia, Canada. Electronic address: [email protected].
  • 6. Department of Psychology, University of British Columbia, Canada; Dajavad Mowifaghian Centre for Brain Health, University of British Columbia, Canada. Electronic address: [email protected].
PMID: 36623432 DOI: 10.1016/j.yhbeh.2022.105297
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.

Keywords
Cognitive flexibility; Female; Prefrontal cortex; Voluntary running; hippocampus.
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