Patel Paresh D, Katz Maor, Karssen Adriaan M, Lyons David M
Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan Medical Center, 5053 Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Psychoneuroendocrinology. 2008 Apr;33(3):360-7. doi: 10.1016/j.psyneuen.2007.12.003. Epub 2008 Jan 28.
Neurobiological studies of stress often focus on the hippocampus where cortisol binds with different affinities to two types of corticosteroid receptors, i.e., mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The hippocampus is involved in learning and memory, and regulates the neuroendocrine stress response, but other brain regions also play a role, especially prefrontal cortex. Here, we examine MR and GR expression in adult squirrel monkey prefrontal cortex and hippocampus after exposure to social stress in infancy or adulthood. In situ hybridization histochemistry with (35)S-labeled squirrel monkey riboprobes and quantitative film autoradiography were used to measure the relative distributions of MR and GR mRNA. Distinct cortical cell layer-specific patterns of MR expression differed from GR expression in three prefrontal regions. The relative distributions of MR and GR also differed in hippocampal Cornu Ammonis (CA) regions. In monkeys exposed to adult social stress compared to the no-stress control, GR expression was diminished in hippocampal CA1 (P=0.021), whereas MR was diminished in cell layer III of ventrolateral prefrontal cortex (P=0.049). In contrast, exposure to early life stress diminished GR but not MR expression in cell layers I and II of dorsolateral prefrontal cortex (P's<0.048). Similar reductions likewise occurred in ventrolateral prefrontal cortex, but the effects of early life stress on GR expression in this region were marginally not significant (P=0.053). These results provide new information on regional differences and the long-term effects of stress on MR and GR distributions in corticolimbic regions that control cognitive and neuroendocrine functions.
应激的神经生物学研究通常聚焦于海马体,皮质醇以不同亲和力与两种类型的皮质类固醇受体结合,即盐皮质激素受体(MR)和糖皮质激素受体(GR)。海马体参与学习和记忆,并调节神经内分泌应激反应,但其他脑区也发挥作用,尤其是前额叶皮质。在此,我们研究了幼年或成年期遭受社会应激后成年松鼠猴前额叶皮质和海马体中MR和GR的表达。使用(35)S标记的松鼠猴核糖探针进行原位杂交组织化学和定量胶片放射自显影来测量MR和GR mRNA的相对分布。在三个前额叶区域,MR表达的不同皮质细胞层特异性模式与GR表达不同。MR和GR的相对分布在海马体的角回(CA)区域也有所不同。与无应激对照组相比,遭受成年期社会应激的猴子海马体CA1区的GR表达减少(P = 0.021),而腹外侧前额叶皮质第III细胞层的MR减少(P = 0.049)。相反,早年应激使背外侧前额叶皮质第I和第II细胞层的GR表达减少,但MR表达未减少(P值<0.048)。腹外侧前额叶皮质也出现类似的减少,但早年应激对该区域GR表达的影响略不显著(P = 0.053)。这些结果为应激对控制认知和神经内分泌功能的皮质边缘区域中MR和GR分布的区域差异及长期影响提供了新信息。