Upregulation of cornichon transcripts in the dorsolateral prefrontal cortex in schizophrenia
Upregulation of cornichon transcripts in the dorsolateral prefrontal cortex in schizophrenia
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DOI：
10.1097/wnr.0b013e32835ad229
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发表时间：
2012-12-05
期刊：
影响因子：
1.7
通讯作者：
Meador-Woodruff, James H.
中科院分区：
文献类型：
--
作者：
Drummond, Jana B.;Simmons, Micah;Meador-Woodruff, James H.
精神分裂症被认为与异常的多巴胺能神经传递有关。谷氨酸受体的AMPA亚型（AMPAR）介导大脑中的快速兴奋性突触传递，并且它们的运输和功能部分地由AMPAR辅助蛋白调节，包括Cornichons（CNIH）和跨膜AMPAR调节蛋白。通过改变这些辅助蛋白的表达，AMPAR的异常调节可以诱导多巴胺能神经传递的变化，从而导致精神分裂症的病理生理学。在这项研究中，通过比较定量实时PCR，在精神分裂症患者组（N=25）和对照组（N=25）的背外侧前额叶皮层中测量了cornichon同源物1-4的转录表达。CNIH-1、CNIH-2和CNIH-3 mRNA表达在精神分裂症中显著上调，CNIH-4表达无变化。为了确定抗精神病药物治疗对这些基因表达的影响，检测了长期接受氟哌啶醇癸酸酯治疗的大鼠额叶皮质中cornichon mRNA的表达，没有发现任何cornichon转录物的变化。CNIH家族基因的异常表达与精神分裂症中cornichon介导的AMPAR运输异常一致，并提出了一种新的机制，有助于这种疾病的病理生理学。NeuroReport 23：1031-1034（C）2012 Wolters Kluwer Health竖条Lippincott威廉姆斯& Wilkins.
Schizophrenia has been proposed to be associated with abnormal glutamatergic neurotransmission. The AMPA subtype of glutamate receptors (AMPARs) mediates fast excitatory synaptic transmission in the brain, and their trafficking and function is regulated in part by AMPAR auxiliary proteins including the cornichons (CNIH) and transmembrane AMPAR-regulatory proteins. Abnormal regulation of AMPARs through altered expression of these auxiliary proteins could induce changes in glutamatergic neurotransmission and thus the pathophysiology of schizophrenia. In this study, transcript expression of cornichon homologs 1-4 was measured in the dorsolateral prefrontal cortex from schizophrenia (N=25) and comparison (N=25) patient groups by comparative quantitative real-time PCR. Significant upregulation of CNIH-1, CNIH-2, and CNIH-3 mRNA expression was found in schizophrenia, with no change in CNIH-4 expression. To determine the effect of antipsychotic treatment on the expression of these genes, cornichon mRNA expression was assayed in the frontal cortex of rats treated chronically with haloperidol decanoate and no changes in any of the cornichon transcripts were found. Abnormal expression of the CNIH family of genes is consistent with cornichon-mediated AMPAR trafficking abnormalities in schizophrenia, and suggests a new mechanism contributing toward the pathophysiology of this illness. NeuroReport 23:1031-1034 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.