SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.

SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.
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人脑背外侧前额皮质和前扣带皮层中的 SNAP-25a/b 同种型水平。

DOI:
10.1159/000441224
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发表时间:
2015
期刊:
Molecular neuropsychiatry
影响因子:
--
通讯作者:
Itakura,Makoto
Itakura,Makoto
中科院分区:
--
文献类型:
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作者:
Thompson,PeterM;Cruz,DianneA;Fucich,ElizabethA;Olukotun,DiannaY;Takahashi,Masami;Itakura,Makoto

文献摘要

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SNAP-25 是一种神经递质囊泡对接蛋白,与注意力缺陷多动障碍、双相情感障碍和精神分裂症等脑部疾病有关。在这个项目中,我们感兴趣的是临床因素是否与 SNAP-25 表达差异相关。我们检查了死后皮层 Brodmann 区 9 (BA9) 和 BA24 (n = 29) 中的 SNAP-25 同工型 mRNA 和蛋白质水平。受试者根据精神病学诊断、临床变量(包括生命最后一周的情绪状态和一生的冲动程度)进行分类。我们发现,与没有酒精使用障碍 (AUD) 的受试者相比,诊断为酒精使用障碍 (AUD) 的受试者的 SNAP-25b BA24 蛋白水平较低。西班牙裔受试者的 SNAP-25a、b 和 BA9 mRNA 水平低于英裔美国人受试者。吸烟的受试者具有总的 SNAP-25 BA9/BA24 比率。与正常对照相比,具有低水平焦虑精神病症状组的受试者具有更高的 SNAP-25a BA24 mRNA,并且高症状组和低症状组都比正常对照具有更高的泛(总)SNAP-25 BA9/BA24 比率。这些数据扩展了我们对 SNAP-25 相关临床因素的理解。他们认为 SNAP-25 总水平和亚型水平可能是超出有限的神经学和精神病学诊断类别的有用生物标志物。
SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories.