Urban Kimberly R, Geng Eric, Bhatnagar Seema, Valentino Rita J
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
The Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA, 19104, USA.
Neurobiol Stress. 2019 Apr 13;10:100165. doi: 10.1016/j.ynstr.2019.100165. eCollection 2019 Feb.
Chronic stress can lead to psychiatric illness characterized by impairments of executive function, implicating the prefrontal cortex as a target of stress-related pathology. Previous studies have shown that various types of chronic stress paradigms reduce dendritic branching, length and spines of medial prefrontal cortex (mPFC) pyramidal neurons. However, these studies largely focused on layer II/III pyramidal neurons in adult male rats with less known about layer V, the site of projection neurons. Because the prefrontal cortex develops throughout adolescence, stress during adolescence may have a greater impact on structure and function than stress occurring during adulthood. Furthermore, females display greater risk of stress-related psychiatric disorders, indicating sex-specific responses to stress. In this study, male and female adolescent (42-48 days old, 4 rats per group) or adult (68-72 days old, 4 rats per group) Sprague-Dawley rats were exposed to 5 days of repeated social stress in the resident-intruder paradigm or control manipulation. We examined dendritic morphology of cells in the mPFC in both layer II/III and Layer V. Repeated social stress resulted in decreased dendritic branching in layer II/III apical dendrites regardless of sex or age. In apical layer V dendrites, stress increased branching in adult males but decreased it in all other groups. Stress resulted in a decrease in dendritic spines in layer V apical dendrites for male adolescents and female adults, and this was mostly due to a decrease in filopodial and mushroom spines for male adolescents, but stubby spines for female adults. In sum, these results suggest that repeated stress reduces complexity and synaptic connectivity in adolescents and female adults in both input and output layers of prelimbic mPFC, but not in male adults. These changes may represent a potential underlying mechanism as to why adolescents and females are more susceptible to the negative cognitive effects of repeated or chronic stress.
慢性应激可导致以执行功能受损为特征的精神疾病，这表明前额叶皮质是应激相关病理的靶点。先前的研究表明，各种类型的慢性应激范式会减少内侧前额叶皮质（mPFC）锥体神经元的树突分支、长度和棘突。然而，这些研究主要集中在成年雄性大鼠的II/III层锥体神经元，而对投射神经元所在的V层了解较少。由于前额叶皮质在整个青春期都在发育，青春期的应激可能比成年期的应激对结构和功能有更大的影响。此外，女性表现出与应激相关的精神疾病的风险更高，表明对压力有性别特异性反应。在本研究中，将雄性和雌性青少年（42 - 48日龄，每组4只大鼠）或成年（68 - 72日龄，每组4只大鼠）的Sprague-Dawley大鼠在居住者-入侵者范式中暴露于5天的重复社会应激或对照操作。我们检查了II/III层和V层mPFC中细胞的树突形态。无论性别或年龄，重复社会应激都会导致II/III层顶端树突的树突分支减少。在V层顶端树突中，应激增加了成年雄性的分支，但在所有其他组中减少了分支。应激导致雄性青少年和成年雌性V层顶端树突的树突棘减少，这主要是由于雄性青少年的丝状伪足和蘑菇状棘减少，而成年雌性的短粗棘减少。总之，这些结果表明，重复应激会降低青春期和成年雌性前边缘mPFC输入和输出层的复杂性和突触连接性，但成年雄性则不会。这些变化可能代表了为什么青少年和女性更容易受到重复或慢性应激的负面认知影响的潜在机制。
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