Periadolescent maturation of the prefrontal cortex is sex-specific and is disrupted by prenatal stress
Article first published online: 4 APR 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Comparative Neurology
Volume 521, Issue 8, pages 1828–1843, 1 June 2013
How to Cite
Markham, J. A., Mullins, S. E. and Koenig, J. I. (2013), Periadolescent maturation of the prefrontal cortex is sex-specific and is disrupted by prenatal stress. J. Comp. Neurol., 521: 1828–1843. doi: 10.1002/cne.23262
- Issue published online: 4 APR 2013
- Article first published online: 4 APR 2013
- Accepted manuscript online: 21 NOV 2012 08:56AM EST
- Manuscript Accepted: 6 NOV 2012
- Manuscript Revised: 1 SEP 2012
- Manuscript Received: 13 APR 2012
- National Institutes of Health. Grant Numbers: K12HD043489, T32 MH067533, MH73826, P50 MH082999
- sex differences;
The prefrontal cortex (PFC) undergoes dramatic, sex-specific maturation during adolescence. Adolescence is a vulnerable window for developing mental illnesses that show significant sexual dimorphisms. Gestational stress is associated with increased risk for both schizophrenia, which is more common among men, and cognitive deficits. We have shown that male, but not female, rats exposed to prenatal stress develop postpubertal deficits in cognitive behaviors supported by the prefrontal cortex. Here we tested the hypothesis that repeated variable prenatal stress during the third week of rat gestation disrupts periadolescent development of prefrontal neurons in a sex-specific fashion. Using Golgi-Cox stained tissue, we compared dendritic arborization and spine density of prelimbic layer III neurons in prenatally stressed and control animals at juvenile (day 20), prepubertal (day 30), postpubertal (day 56), and adult (day 90) ages (N = 115). Dendritic ramification followed a sex-specific pattern that was disrupted during adolescence in prenatally stressed males, but not in females. In contrast, the impact of prenatal stress on the female PFC was not evident until adulthood. Prenatal stress also caused reductions in brain and body weights, and the latter effect was more pronounced among males. Additionally, there was a trend toward reduced testosterone levels for adult prenatally stressed males. Our findings indicate that, similarly to humans, the rat PFC undergoes sex-specific development during adolescence and furthermore that this process is disrupted by prenatal stress. These findings may be relevant to both the development of normal sex differences in cognition as well as differential male–female vulnerability to psychiatric conditions. J. Comp. J. Comp. Neurol. 521:1828–1843, 2013. © 2012 Wiley Periodicals, Inc.