ALDH4A1 expression levels are elevated in postmortem brains of patients with schizophrenia and are associated with genetic variants in enzymes related to proline metabolism
ALDH4A1 expression levels are elevated in postmortem brains of patients with schizophrenia and are associated with genetic variants in enzymes related to proline metabolism
复制标题
精神分裂症患者死后大脑中 ALDH4A1 表达水平升高，并且与脯氨酸代谢相关酶的遗传变异有关
DOI：
10.1016/j.jpsychires.2020.02.001
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发表时间：
2020
影响因子：
4.8
通讯作者：
Yabe Hirooki
中科院分区：
文献类型：
--
作者：
Nagaoka Atsuko;Kunii Yasuto;Hino Mizuki;Izumi Ryuta;Nagashima Chisato;Takeshima Akari;Sainouchi Makoto;Nawa Hiroyuki;Kakita Akiyoshi;Yabe Hirooki
背景精神分裂症的分子机制尚不清楚，我们最近发现精神分裂症患者死后前额皮质（PFC）中多种蛋白质发生显着改变，其中乙醛脱氢酶4家族成员A1（ALDH4A1）尤其升高。在本研究中，我们旨在研究 ALDH4A1 在 PFC 和颞上回 (STG) 中的表达，并阐明精神分裂症风险等位基因与精神分裂症患者死后大脑中分子表达谱之间的功能相关性。 方法 检测 24 例精神分裂症患者死后大脑中 PFC 和 STG 中 ALDH4A1 蛋白的表达水平 使用酶联免疫吸附测定对精神分裂症、8 名双相情感障碍患者和 32 名对照进行评估。此外，我们还探讨了 ALDH4A1 表达与脯氨酸代谢相关酶的遗传变异之间的关联，包括 ALDH4A1（精神分裂症 [n = 22]、双相情感障碍 [n = 6]、对照 [n = 11]）。结果 精神分裂症患者的 PFC 和 STG 中 ALDH4A1 水平均显着升高，并且双相情感障碍患者倾向于升高 紊乱。此外，PFC中的ALDH4A1表达水平与以下三个单核苷酸多态性显着相关：rs10882639、rs33823、rs153508。我们还在死后大脑的假定星形胶质细胞子集中的线粒体中发现了 ALDH4A1 的部分共表达。局限性我们的研究人群相对较小，特别是对于基因研究而言。结论这些发现表明 ALDH4A1 表达的改变可能反映了精神分裂症和双相情感障碍发病机制的潜在分子机制，并可能有助于新药的开发 疗法。
BackgroundThe molecular mechanisms underlying schizophrenia remain largely unclear, and we recently identified multiple proteins significantly altered in the postmortem prefrontal cortex (PFC) of schizophrenia patients amongst which aldehyde dehydrogenase 4 family member A1 (ALDH4A1) was especially elevated. In this study, we aimed to investigate the expression of ALDH4A1 in the PFC and superior temporal gyrus (STG) and to elucidate functional correlations between schizophrenia risk alleles and molecular expression profiles in the postmortem brains of patients with schizophrenia.MethodsThe levels of ALDH4A1 protein expression in the PFC and STG in postmortem brains from 24 patients with schizophrenia, 8 patients with bipolar disorder, and 32 controls were assessed using enzyme-linked immunosorbent assay. Moreover, we explored the associations between ALDH4A1 expression and genetic variants in enzymes associated with proline metabolism, including ALDH4A1 (schizophrenia [n = 22], bipolar disorder [n = 6], controls [n = 11]).ResultsALDH4A1 levels were significantly elevated in both the PFC and STG in patients with schizophrenia and tended to elevate in patients with bipolar disorder. Furthermore, ALDH4A1 expression levels in the PFC were significantly associated with the following three single-nucleotide polymorphisms: rs10882639, rs33823, rs153508. We also found partial coexpression of ALDH4A1 in mitochondria in a subset of putative astrocytes of postmortem brain.LimitationsOur study population was relatively small, particularly for a genetic study.ConclusionThese findings indicate that altered expression of ALDH4A1 may reflect the potential molecular mechanisms underlying the pathogenesis of schizophrenia and bipolar disorder, and may aid in the development of novel drug therapies.