Perinatal adverse experience programs social and emotional behavioral traits and is a major risk factor for the development of behavioral and psychiatric disorders. Little information is available on how adversity to the mother prior to her first pregnancy (preconception stress, PCS) may affect brain structural development, which may underlie behavioral dysfunction in the offspring. Moreover, little is known about possible sex-dependent consequences of PCS in the offspring. This study examined spine number/density and dendritic length/complexity of layer II/III pyramidal neurons in the anterior cingulate (ACd), prelimbic/infralimbic (PL/IL) and orbitofrontal cortex (OFC) of male and female rats born to mothers exposed to unpredictable variable stress at different time points prior to reproduction. Our main findings are that in line with our hypothesis adversity to the mother before her pregnancy results in highly complex changes in neuronal morphology in the medial prefrontal, but not in the orbitofrontal cortical regions of her future offspring that persist into adulthood. Moreover, our study revealed that (1) in the PCS2 group (offspring of dams mated two weeks after stress) spine numbers and dendritic length and complexity were increased in response to PCS in the ACd and PL/IL, (2) these regional effects depended on the temporal proximity of adversity and conception, (3) in the ACd of the PCS2 group only males and the left hemispheres were affected. We speculate that these transgenerational brain structural changes are mediated by stress-induced epigenetic (re)programming of future gene activity in the oocyte.
Bibliographical noteFunding Information:
The authors would like to appreciate the expert technical assistance of Susann Becker with the histological procedures. This work was funded by the German-Israeli Foundation for Scientific Research and Development, and by grants from the Bundesministerium fÃ¼r Bildung und Forschung (BMBF) Research Consortium UBICA and Research Consortium TRANS-GEN, by the Center for Behavioral Brain Sciences (CBBS) and by the European Regional Development Fund (ERDF).
© 2014, Springer-Verlag Berlin Heidelberg.
- Pregestational stress
- Prereproductive stress
- Synaptic development
ASJC Scopus subject areas
- Neuroscience (all)