Tatro Erick T, Everall Ian P, Masliah Eliezer, Hult Britta J, Lucero Ginger, Chana Gursharan, Soontornniyomkij Virawudh, Achim Cristian L
Department of Psychiatry-0603, University of California at San Diego, La Jolla, San Diego, CA 92093-0603, USA.
J Neuroimmune Pharmacol. 2009 Jun;4(2):218-26. doi: 10.1007/s11481-009-9146-6. Epub 2009 Feb 6.
Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD) than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression in autopsy tissues from the frontal cortical gray matter. The study cases were divided into five groups: control, MDD, MDD with psychosis, HIV(+), and HIV(+) with MDD. Gene expression and protein levels were determined by real-time PCR and Western blot analysis of fresh frozen tissues. Genotyping of previously published alleles of the FKBP5 gene was also performed. We found correlation of upregulation of both immunophilins in the HIV-infected groups. In the HIV(+) population with MDD, FKBP4 expression is significantly higher while FKBP5 is more variable. After analyzing the FKBP5 gene for single nucleotide polymorphisms, we found that rs3800373 CC genotype is more frequent in the MDD and MDD/Psychosis groups. We hypothesized that the levels of FKBP51, as modulator of the nuclear translocation of GR, would be lower in MDD. Instead, an increase in FKBP51 at both the transcript (FKBP5) and protein level correlated with MDD. Increased FKBP4 expression of correlated to HIV(+)MDD but not to HIV without MDD.
感染人类免疫缺陷病毒（HIV）的患者患重度抑郁症（MDD）的风险高于普通人群。免疫亲和蛋白FKBP51和FKBP52在皮质神经元中表达，并调节糖皮质激素受体（GR）的功能。先前的报道表明，编码FKBP51的FKBP5基因中的遗传变异与精神疾病有关。我们试图确定免疫亲和蛋白在HIV感染中是否上调。为了确定FKBP52和FKBP51是否与MDD和/或HIV相关，我们比较了额叶皮质灰质尸检组织中的蛋白质和基因表达。研究病例分为五组：对照组、MDD组、伴有精神病的MDD组、HIV阳性组和伴有MDD的HIV阳性组。通过对新鲜冷冻组织进行实时PCR和蛋白质印迹分析来确定基因表达和蛋白质水平。还对FKBP5基因先前公布的等位基因进行了基因分型。我们发现在HIV感染组中两种免疫亲和蛋白均上调。在伴有MDD的HIV阳性人群中，FKBP4表达显著更高，而FKBP5的变化更大。在分析FKBP5基因的单核苷酸多态性后，我们发现rs3800373 CC基因型在MDD组和MDD/精神病组中更常见。我们假设，作为GR核转位调节剂的FKBP51水平在MDD中会更低。相反，转录本（FKBP5）和蛋白质水平的FKBP51增加均与MDD相关。FKBP4表达增加与HIV（+）MDD相关，但与无MDD的HIV无关。
