BACKGROUND The 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. METHODS The 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]). RESULTS ALDH4A1 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. LIMITATIONS Our study population was relatively small, particularly for a genetic study. CONCLUSION These 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.

中文翻译：

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ALDH4A1 表达水平在精神分裂症患者的死后大脑中升高，并且与脯氨酸代谢相关酶的遗传变异有关。

背景精神分裂症的分子机制在很大程度上仍不清楚，我们最近在精神分裂症患者的死后前额叶皮层 (PFC) 中发现了多种蛋白质显着改变，其中醛脱氢酶 4 家族成员 A1 (ALDH4A1) 特别升高。在这项研究中，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。方法采用酶联免疫吸附试验评估24名精神分裂症患者、8名双相情感障碍患者和32名对照者死后大脑PFC和STG中ALDH4A1蛋白表达水平。而且，我们探讨了 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 PFC 和 STG 中 ALDH4A1 水平显着升高，而双相情感障碍患者则趋于升高。此外，PFC 中 ALDH4A1 的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发现了 ALDH4A1 在线粒体中的部分共表达。局限性 我们的研究人群相对较小，特别是对于基因研究。