Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex
Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex
复制标题
DOI：
10.1007/s00429-014-0940-4
复制
发表时间：
2016-03-01
影响因子：
3.1
通讯作者：
Poeggel, Gerd
中科院分区：
文献类型：
--
作者：
Bock, Joerg;Poeschel, Julia;Poeggel, Gerd
围产期不良经历影响了社会和情绪行为特征，是行为和精神障碍发展的主要危险因素。关于母亲在第一次怀孕前遭遇的逆境(预孕应激，PCS)如何影响大脑结构发育，这可能是后代行为障碍的基础，目前还没有什么信息。此外，对于PCS在后代中可能产生的性别依赖后果，人们知之甚少。本研究检测了雌性和雄性大鼠在生殖前不同时间点暴露于不可预测的可变应激状态下出生的雄性和雌性大鼠的前扣带回(ACD)、前缘/下缘(PL/IL)和眶前叶皮质(OFC)内II/III层锥体神经元的棘数/密度和树突长度/复杂性。我们的主要发现是，与我们的假设一致，怀孕前母亲的逆境会导致前额内侧神经元形态的高度复杂变化，但不会在她未来后代的眶前皮质区域持续到成年。此外，我们的研究还表明：(1)PCS2组(应激后两周交配的后代)ACD和PL/IL中的PCS反应增加了棘突数目、树突长度和复杂性；(2)这些区域效应依赖于逆境和受孕的时间接近；(3)在PCS2组的ACD中，只有男性和左半球受到影响。我们推测，这些跨代脑结构变化是由应激诱导的卵母细胞未来基因活动的表观遗传(Re)编程所介导的。
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.