Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1139-43. doi: 10.1016/j.pnpbp.2011.03.016. Epub 2011 Mar 29.
Many neuroimaging studies have revealed structural abnormalities in the superior temporal gyrus (STG) in schizophrenia (Kasai et al., 2003a, 2003b; Sun et al., 2009). Neurophysiological studies of mismatch negativities (MMN) generated in the STG have suggested impaired function of N-methyl-d-aspartate (NMDA) receptors (Javitt et al., 1996). Although many postmortem studies have been conducted on the pathogenesis of schizophrenia, relatively few reports have studied molecular alterations in the STG (Bowden et al., 2008; Deng and Huang, 2006; Kang et al., 2009; Katsel et al., 2005; Le Corre et al., 2000; Nudmamud and Reynolds, 2001; Sokolov et al., 2000). The STG shows pronounced changes in gene expression when compared to other regions implicated in schizophrenia (Katsel et al., 2005). Dopamine and a cAMP-regulated phosphoprotein of molecular weight 32kDa (DARPP-32) is thought to be closely associated with pathophysiological changes in the dopamine and glutamate systems in schizophrenia because, when activated by phosphorylation, DARPP-32 acts as a critical regulator of D1 dopamine receptor and NMDA receptor activity (Greengard et al., 1999). The molecular pathways involving DARPP-32 appear important in the pathogenesis of schizophrenia. Here, we show dramatic alterations in DARPP-32 expression in the STG of postmortem brains from patients with schizophrenia. To clarify the detailed histological and cellular expression of DARPP-32 in the STG in schizophrenia, we immunohistochemically examined postmortem brains by using specific antibodies. We compared the density of immunoreactive cells of the STG (BA22) from 11 schizophrenia patients with those from 11 age- and sex-matched controls, and found significantly lower densities of DARPP-32-immunoreactive (IR) cells and threonine (Thr) 34-phosphorylated DARPP-32-IR cells in the STG in the schizophrenia group. Thus, the DARPP-32-related pathogenesis in schizophrenia may be more severe in the STG than previously found in the prefrontal cortex.
许多神经影像学研究揭示了精神分裂症患者颞上回（STG）的结构异常（Kasai 等人，2003a，2003b；Sun 等人，2009）。对 STG 中产生的失匹配负波（MMN）的神经生理学研究表明，N-甲基-D-天冬氨酸（NMDA）受体功能受损（Javitt 等人，1996）。尽管许多关于精神分裂症发病机制的尸检研究已经进行，但很少有研究报道 STG 中的分子改变（Bowden 等人，2008；Deng 和 Huang，2006；Kang 等人，2009；Katsel 等人，2005；Le Corre 等人，2000；Nudmamud 和 Reynolds，2001；Sokolov 等人，2000）。与其他涉及精神分裂症的区域相比，STG 显示出明显的基因表达变化（Katsel 等人，2005）。多巴胺和 cAMP 调节的 32kDa 磷酸蛋白（DARPP-32）被认为与精神分裂症中多巴胺和谷氨酸系统的病理生理变化密切相关，因为 DARPP-32 被磷酸化激活后，作为 D1 多巴胺受体和 NMDA 受体活性的关键调节剂（Greengard 等人，1999）。涉及 DARPP-32 的分子途径似乎在精神分裂症的发病机制中很重要。在这里，我们显示精神分裂症患者死后大脑的 STG 中 DARPP-32 表达的显著改变。为了阐明精神分裂症中 STG 中 DARPP-32 的详细组织学和细胞表达，我们使用特异性抗体对死后大脑进行了免疫组织化学检查。我们比较了 11 名精神分裂症患者和 11 名年龄和性别匹配的对照者 STG（BA22）的免疫反应细胞密度，发现精神分裂症组 STG 中 DARPP-32 免疫反应（IR）细胞和苏氨酸（Thr）34 磷酸化 DARPP-32-IR 细胞的密度显著降低。因此，与精神分裂症相关的 DARPP-32 发病机制在 STG 中的严重程度可能比以前在额前皮质中发现的更为严重。
