TGFBR2 gene expression and genetic association with schizophrenia

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• 作者：Shusuke Numata ; Shu-ichi Ueno ; Jun-ichi Iga ; Ken Yamauchi ; Song Hongwei ; Ryota Hashimoto ; Masatoshi Takeda ; Hiroshi Kunugi ; Mitsuo Itakura ; Tetsuro Ohmori
• 关键词：TGFBR2 ; Gene expression ; Leukocytes ; Association analysis ; Schizophrenia
• 刊名：Journal of Psychiatric Research
• 出版年：2008
• 期刊代码：169_00223956
• 类别：med
• 出版时间：May 2008
• 卷：42
• 期：6
• 页码：425-432
• 文件大小：254 K

摘要

There are quantitative differences in 5-HTR expression in schizophrenia, shown using in situ hybridization (ISH), RT-PCR, and receptor autoradiography. For example, in prefrontal cortex, 5-HT_1AR densities but not 5-HT_1AR mRNA are elevated, whereas 5-HT_2AR mRNA and binding sites are both reduced. Initial data suggest that 5-HT_2CR mRNA is unaltered in schizophrenia. The biological significance of these changes depends in part on the detailed localization of each 5-HTR subtype. We are therefore using cellular ISH to map the differential expression of 5-HTRs to clarify their position in the neural circuitry. For example, in cortex 5-HT_1AR are expressed by pyramidal neurons, 5-HT_2AR by pyramidal and interneurons, and 5-HT_2CR by scattered, unidentified cells.

In addition to these disease-associated changes, 5-HTR expression is affected by antipsychotic drugs. In particular clozapine, but not haloperidol, down-regulates 5-HT_2AR gene expression, but preliminary data suggest that it does not affect 5-HT_2CR mRNA nor 5-HT₇R mRNA. Complicating the relationship between 5-HT₂ receptors, schizophrenia, and antipsychotic drugs, it has been reported that polymorphic variants of 5-HT₂R may be risk factors for the disease and for clozapine non-response. It was proposed that these effects may be mediated via allelic differences in gene expression. However, early results in human brain of individuals genotyped for 5-HT_2AR T102C status do not support this hypothesis.