Altar C Anthony, Jurata Linda W, Charles Vin, Lemire Andrew, Liu Peng, Bukhman Yury, Young Theresa A, Bullard Jeff, Yokoe Hiroko, Webster Maree J, Knable Michael B, Brockman Jeffrey A
Psychiatric Genomics, Inc., Gaithersburg, Maryland 20878, USA.
Biol Psychiatry. 2005 Jul 15;58(2):85-96. doi: 10.1016/j.biopsych.2005.03.031.
Hippocampal dentate granule neurons are altered in schizophrenia, but it is unknown if their gene expressions change in schizophrenia or other psychiatric diseases.
Laser-captured dentate granule neurons from two groups of schizophrenia and control cases and from major depression and bipolar disease cases were examined for alterations in gene expression using complementary DNA (cDNA) microarrays and reverse transcription polymerase chain reaction (RT-PCR).
Compared with 24 control cases, the 22 schizophrenia patients in both groups revealed decreases in clusters of genes that encode for protein turnover (proteasome subunits and ubiquitin), mitochondrial oxidative energy metabolism (isocitrate, lactate, malate, nicotinamide adenine dinucleotide [NADH], and succinate dehydrogenases; cytochrome C oxidase; adenosine triphosphate [ATP] synthase), and genes associated with neurite outgrowth, cytoskeletal proteins, and synapse plasticity. These changes were not obtained in 9 bipolar cases or 10 major depression cases and were not associated with age, sex, brain weight, body weight, postmortem interval, or drug history. Brain pH contributed to the variance of some genes but was mostly independent of the disease effect.
Decreases in hippocampal neuron gene expression are consistent with brain imaging and microarray studies of the frontal cortex in schizophrenia. A mitochondrial and ubiquitin-proteasome hypofunctioning of dentate granule neurons may contribute to the deficits of schizophrenia.
精神分裂症患者海马齿状颗粒神经元会发生改变，但尚不清楚其基因表达在精神分裂症或其他精神疾病中是否会发生变化。
使用互补DNA（cDNA）微阵列和逆转录聚合酶链反应（RT-PCR），对两组精神分裂症患者及对照组、重度抑郁症患者及双相情感障碍患者的激光捕获齿状颗粒神经元进行基因表达变化检测。
与24例对照病例相比，两组共22例精神分裂症患者编码蛋白质周转（蛋白酶体亚基和泛素）、线粒体氧化能量代谢（异柠檬酸、乳酸、苹果酸、烟酰胺腺嘌呤二核苷酸[NADH]和琥珀酸脱氢酶；细胞色素C氧化酶；三磷酸腺苷[ATP]合酶）以及与神经突生长、细胞骨架蛋白和突触可塑性相关的基因簇表达均降低。9例双相情感障碍病例和10例重度抑郁症病例未出现这些变化，且这些变化与年龄、性别、脑重量、体重、死后间隔时间或用药史无关。脑pH值对某些基因的差异有影响，但大多独立于疾病效应。
海马神经元基因表达降低与精神分裂症患者额叶皮质的脑成像和微阵列研究结果一致。齿状颗粒神经元的线粒体和泛素-蛋白酶体功能减退可能导致精神分裂症的缺陷。
