Developmental and adult stress: effects of steroids and neurosteroids

Abstract

In humans, exposure to early life adversity has profound implications for susceptibility to developing neuropsychiatric disorders later in life. Studies in rodents have shown that stress experienced during early postnatal life can have lasting effects on brain development. Glucocorticoids and sex steroids are produced in endocrine glands and the brain from cholesterol; these molecules bind to nuclear and membrane-associated steroid receptors. Unlike other steroids that can also be made in the brain, neurosteroids bind specifically to neurotransmitter receptors, not steroid receptors. The relationships among steroids, neurosteroids, and stress are multifaceted and not yet fully understood. However, studies demonstrating altered levels of progestogens, androgens, estrogens, glucocorticoids, and their neuroactive metabolites in both developmental and adult stress paradigms strongly suggest that these molecules may be important players in stress effects on brain circuits and behavior. In this review, we discuss the influence of developmental and adult stress on various components of the brain, including neurons, glia, and perineuronal nets, with a focus on sex steroids and neurosteroids. Gaining an enhanced understanding of how early adversity impacts the intricate systems of brain steroid and neurosteroid regulation could prove instrumental in identifying novel therapeutic targets for stress-related conditions.

Keywords:

• Sex steroids
• glucocorticoids
• neurosteroids
• perineuronal nets
• sex differences
• glia

Acknowledgements

The authors thank Casey Brown for helpful comments on the manuscript and Biorender for assistance with the figure schematics.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by R01MH117459-01 to EG.

Notes on contributors

Isha R. Gore

Isha R. Gore is a PhD student at the Princeton Neuroscience Institute (PNI) studying the effects of stress on neural mechanisms underlying avoidance behavior in mice. Prior to joining PNI, Gore received a Master’s degree from Columbia University.

Elizabeth Gould

Elizabeth Gould, PhD is a Professor of Neuroscience and head of laboratory at the Princeton Neuroscience Institute. Her lab focuses on plasticity mechanisms affected by genes, experience, and steroids in developing and adult mice. Prior to joining the Princeton faculty, Gould received her PhD from UCLA and was a postdoctoral fellow and assistant professor at The Rockefeller University.