Splinter, T. F. | bioRxiv Science

bioRxiv2022

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

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 wildtype (Val/Val)) influenced the ability of voluntary running to increase 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. HighlightsO_LIBDNF Met/Met mice performed worse than BDNF Val/Val mice in middle-age C_LIO_LIAerobic training (AT) increased cognitive performance in BDNF Met/Met mice C_LIO_LIAT increased neurogenesis in middle-aged BDNF Val/Val mice only C_LIO_LIFemale BDNF Val/Val mice had better cognitive flexibility than males regardless of AT C_LIO_LIAT increased more mature new neurons in middle-aged female mice C_LI

neuroscience↗

bioRxiv2021

Harnessing the Power of Sex Differences: What a Difference Ten Years Did Not Make

Sex differences exist in many neurological and psychiatric diseases. Mandates have been initiated across funding agencies for research to include males and females. What has been lacking in the literature is a detailed assessment of how sex is incorporated into the design (e.g. balanced design) and into the analyses (e.g. covariate). We surveyed papers in 2009 and 2019 across six journals in Neuroscience and Psychiatry. There was a 30% increase in the percentage of papers that included both sexes to 68% in 2019. Despite this increase, in 2019 only 19% of studies used an optimal design for discovery of possible sex differences and only 5% analyzed sex as a discovery variable. Here we show that little progress has been made in harnessing the power that sex differences can afford in research for discovery and therapeutic potential for neurological and psychiatric disease to improve the health of men, women and gender diverse individuals. Highlights68% of Neuroscience and Psychiatry papers reported the use of both sexes in 2019 Only 19% of studies in 2019 used sex consistently throughout the study analyses Of the studies that used males and females, 59% did not include sex in the analyses Only 5% of studies in 2019 used sex as a discovery variable in their analyses Male only papers were 8.4 times more prevalent than female-only papers

neuroscience↗