Expression of Interneuron Markers in the Dorsolateral Prefrontal Cortex of the Developing Human and in Schizophrenia
Expression of Interneuron Markers in the Dorsolateral Prefrontal Cortex of the Developing Human and in Schizophrenia
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DOI：
10.1176/appi.ajp.2010.09060784
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发表时间：
2010-12-01
影响因子：
17.7
通讯作者：
Weickert, Cynthia Shannon
中科院分区：
文献类型：
--
作者：
Fung, Samantha J.;Webster, Maree J.;Weickert, Cynthia Shannon
目的：精神分裂症症状在青春期后期的发作暗示了该疾病的神经发育轨迹。事实上，γ-氨基丁酸（GABA）抑制系统显示出长期的发展，GABA能缺陷被广泛复制在死后精神分裂症的研究。作者检查了几种中间神经元标记物在出生后人类发育和精神分裂症中的表达，以评估某些中间神经元亚群的长期发育是否可能与精神分裂症的特定脆弱性相关。方法：从6周龄至49岁的个体（N=68）的背外侧前额叶皮质以及正常对照组和精神分裂症患者的队列中死后提取RNA（N=74，37对）。通过定量逆转录-聚合酶链反应测定小清蛋白、胆囊收缩素、生长抑素、神经肽Y、钙视网膜蛋白、钙结合蛋白和血管活性肠肽的表达水平。结果：中间神经元标记基因表达谱有三种：一种是表达量增加，另一种是表达量增加。（小清蛋白、胆囊收缩素）或降低（生长抑素，钙视网膜蛋白，神经肽Y）的表达在出生后的生活，与最显着的变化出现在前几年达到平台期之前;或在幼儿期增加到峰值表达，然后降低（钙结合蛋白，血管活性肠肽）。所有基因的mRNA表达，除了钙结合蛋白（增加），显示减少（8%-31%）在精神分裂症。生长抑素表现出最显着的减少（31%）在schizophrenia.Conclusions：它似乎是一个异质性的中间神经元的人口牵连在精神分裂症。需要进一步的研究来确定是否特定的中间神经元亚群被改变，或者是否共同或不同的上游通路负责精神分裂症中的中间神经元缺陷。
Objective: The onset of schizophrenia symptoms in late adolescence implies a neurodevelopmental trajectory for the disease. Indeed, the gamma-aminobutyric acid (GABA) inhibitory system shows protracted development, and GABA-ergic deficits are widely replicated in postmortem schizophrenia studies. The authors examined expression of several interneuron markers across postnatal human development and in schizophrenia to assess whether protracted development of certain interneuron subpopulations may be associated with a particular vulnerability in schizophrenia.Method: RNA was extracted postmortem from dorsolateral prefrontal cortex of individuals from age 6 weeks to 49 years (N=68) and from a cohort of normal comparison subjects and schizophrenia patients (N=74, 37 pairs). Expression levels of parvalbumin, cholecystokinin, somatostatin, neuropeptide Y, calretinin, calbindin, and vasoactive intestinal peptide were measured by quantitative reverse transcription-polymerase chain reaction. Changes in calretinin protein levels were examined by Western blot.Results: Interneuron marker genes followed one of three general expression profiles: either increasing (parvalbumin, cholecystokinin) or decreasing (somatostatin, calretinin, neuropeptide Y) in expression over postnatal life, with the most dramatic changes seen in the first few years before reaching a plateau; or increasing to peak expression in the toddler years before decreasing (calbindin, vasoactive intestinal peptide). mRNA expression of all genes, with the exception of calbindin (which increased), showed a reduction (8%-31%) in schizophrenia. Somatostatin showed the most dramatic reduction (31%) in schizophrenia.Conclusions: It appears that a heterogeneous population of interneurons is implicated in schizophrenia. Further studies are needed to determine whether specific interneuron subpopulations are altered or whether common or distinct upstream pathways are responsible for interneuron deficits in schizophrenia.