 17th
International Conference of the Society of Neuroscientists of Africa Marrakesh-Morocco April, 17-20, 2025 |
Keynote 1
Stress across generations:
Mechanisms for altering brain development
Tracy L. Bale
Department of Psychiatry Sex Differences Research University of Colorado
Parental lifetime experiences to
perturbations such as stress, infection, malnutrition, and advanced age
are linked with an increased risk for offspring disease, including a
strong association with neuropsychiatric disorders. In somatic cells
involved in germ cell maturation, lasting changes to cellular function
and energy metabolism are found following cumulative stress or trauma.
We have focused on identifying the causal biological mechanisms whereby
information in the environment can be transmitted to germ cells and
ultimately alter the course of embryo development, affecting the brain
health of the next generation. In our preclinical animal studies, we
examine causal roles for somatic-to-germline transmission of stress
signals capable of altering the rate of fetal neurodevelopment via
specific types of secreted nanoparticles, or extracellular vesicles
(EVs). In the somatic cells along the male reproductive tract, we
previously identified broad histone and transcriptomic alterations in
mouse epididymal epithelial cells (EECs) in vivo and in vitro. Further,
these cells produced significant changes in the secreted EV proteome
cargo and when incubated with sperm, these EVs increase sperm motility
via targeted enhancement of mitochondrial respiration. Following
fertilization, these sperm produce embryos with faster rates of
development, including for the brain. As adults, these mice have a
reduced stress reactivity, altering their ability to homeostatically
respond to a changing environment. Translationally, we have found
similar effects of chronic perceived stress changes in human sperm
motility and EV cargo, suggesting that stress has a significant effect
on reproductive processes to alter the embryonic developmental
trajectory. Together, these studies support a causal importance of EV
sperm interactions in the intergenerational delivery of environmental
signals critical to brain development.
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