Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex.
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.
Research Group "Epigenetics and Structural Plasticity", Institute of Biology, Otto von Guericke University, Magdeburg, Germany. joerg.bock@ovgu.de.|Center For Behavioral Brain Science (CBBS), Magdeburg, Germany. joerg.bock@ovgu.de.|Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Magdeburg, Germany. joerg.bock@ovgu.de.
Joerg
J
Bock
Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany.
Julia
J
Poeschel
Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany.
Julia
J
Schindler
Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany.
Florian
F
Börner
Department of Psychology, University of Haifa, 31905, Haifa, Israel.
Alice
A
Shachar-Dadon
Department of Psychology, University of Haifa, 31905, Haifa, Israel.
Neta
N
Ferdman
Department of Psychology, University of Haifa, 31905, Haifa, Israel.|Department of Psychiatry, Division of Molecular Therapeutics, Columbia University, New York, USA.
Inna
I
Gaisler-Salomon
Department of Psychology, University of Haifa, 31905, Haifa, Israel.
Micah
M
Leshem
Center For Behavioral Brain Science (CBBS), Magdeburg, Germany. katharina.braun@ovgu.de.|Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University, Magdeburg, Germany. katharina.braun@ovgu.de.
Katharina
K
Braun
Institute for Biology, Human Biology, University of Leipzig, 04103, Leipzig, Germany.
Gerd
G
Poeggel
D000818:Animals; D001921:Brain; D003712:Dendrites / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology*; D004644:Emotions; D005260:Female; D006179:Gyrus Cinguli; D008297:Male; D017397:Prefrontal Cortex / Q000502:physiology*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013315:Stress, Psychological / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
Prefrontal; Pregestational stress; Prereproductive stress; Synaptic development; Transgenerational