Perlman William R, Tomaskovic-Crook Eva, Montague Deidra M, Webster Maree J, Rubinow David R, Kleinman Joel E, Weickert Cynthia Shannon
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, MD 20892-1385, USA.
Biol Psychiatry. 2005 Nov 15;58(10):812-24. doi: 10.1016/j.biopsych.2005.04.047. Epub 2005 Aug 22.
Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor alpha (ERalpha) mRNA levels may exist in MMI patients.
We used Northern blot analysis to survey the expression of ERalpha mRNA transcripts in brain and body, detected by our human ERalpha riboprobe and in situ hybridization, to examine the expression pattern and quantify ERalpha mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects.
Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ERalpha mRNA transcript. By in situ hybridization, ERalpha mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERalpha mRNA expression in male compared with female MDD subjects and reduced ERalpha mRNA levels in the dentate gyrus of schizophrenics compared with control subjects.
Our results suggest that alterations in ERalpha mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.
在主要精神疾病（MMI）中已描述了性别差异。背外侧前额叶皮质（DLPFC）和海马体是雌激素敏感的脑区，在MMI患者中其结构和功能会发生改变。我们假设MMI患者的DLPFC和海马体雌激素受体α（ERα）mRNA水平可能存在性别特异性改变。
我们使用Northern印迹分析来检测脑和身体中ERα mRNA转录本的表达，通过我们的人ERα核糖探针和原位杂交进行检测，以检查重度抑郁症（MDD）、精神分裂症和双相情感障碍患者与正常对照受试者相比，DLPFC和前海马体中ERα mRNA的表达模式并定量其水平。
Northern印迹显示5 kb ERα mRNA转录本的表达水平存在脑区特异性差异。通过原位杂交，在所有受试者的DLPFC各层和所有海马亚区均检测到ERα mRNA。我们发现，与女性MDD受试者相比，男性MDD受试者的DLPFC中ERα mRNA表达更高；与对照受试者相比，精神分裂症患者齿状回中的ERα mRNA水平降低。
我们的结果表明，男性和女性MDD患者以及精神分裂症患者的不同端脑区域中均存在ERα mRNA水平的改变。
