Differential neuregulin 1 cleavage in the prefrontal cortex and hippocampus in schizophrenia and bipolar disorder: preliminary findings.
Differential neuregulin 1 cleavage in the prefrontal cortex and hippocampus in schizophrenia and bipolar disorder: preliminary findings.
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DOI：
10.1371/journal.pone.0036431
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Walss-Bass C
中科院分区：
文献类型：
--
作者：
Marballi K;Cruz D;Thompson P;Walss-Bass C
神经调节蛋白1 （NRG1）是精神分裂症（SCZ）和双相情感障碍（BPD）的关键候选易感基因。NRG1跨膜蛋白的功能受卵裂调节。在缺乏nrg1切割酶（如BACE1和γ分泌酶）表达的小鼠模型中，膜结合nrg1切割的改变已被证明与行为障碍有关。我们试图确定NRG1切割和相关酶的改变是否发生在SCZ和BPD患者中。利用人死后的大脑，我们评估了NRG1切割产物的蛋白表达以及细胞膜外（BACE1, ADAM17, ADAM19）和内（ps1 - γ分泌酶）切割酶的蛋白表达。我们使用了三个不同的队列（对照组、SCZ和BPD）和两个不同的大脑区域：ba9 -前额皮质（对照组（n = 6）、SCZ （n = 6）和BPD (n = 6)）和海马（对照组（n = 5）、SCZ （n = 6）和BPD (n = 6)）。在BA9中，SCZ队列中NRG1 n端片段相对于全长的比例显著上调（Bonferroni检验，p = 0.011）。在SCZ队列中，ADAM17与全长NRG1水平呈负相关（r = -0.926, p = 0.008）。在海马中，我们发现与对照组相比，两个受影响组的可溶性50 kDa NRG1片段水平显著降低（Bonferroni检验，p = 0.0018）。我们还使用双相症状和体征量表（BISS）和Montgomery Åsberg抑郁评定量表（MADRS）检查了特定症状标准与NRG1分裂的关系。我们的结果显示ADAM19与精神病呈正相关（r = 0.595 p = 0.019）；PS1与躁狂症（r = 0.535, p = 0.040）；海马区PS1伴抑郁（r = 0.567, p = 0.027），海马区BACE1伴焦虑（r = 0.608, p = 0.03）。我们的初步研究结果表明，SCZ和BPD患者的NRG1切割存在区域特异性改变。这些变化可能与这些精神障碍的特定症状有关。
Neuregulin 1 (NRG1) is a key candidate susceptibility gene for both schizophrenia (SCZ) and bipolar disorder (BPD). The function of the NRG1 transmembrane proteins is regulated by cleavage. Alteration of membrane bound-NRG1 cleavage has been previously shown to be associated with behavioral impairments in mouse models lacking expression of NRG1-cleavage enzymes such as BACE1 and gamma secretase. We sought to determine whether alterations in NRG1 cleavage and associated enzymes occur in patients with SCZ and BPD. Using human postmortem brain, we evaluated protein expression of NRG1 cleavage products and enzymes that cleave at the external (BACE1, ADAM17, ADAM19) and internal (PS1-gamma secretase) sides of the cell membrane. We used three different cohorts (Controls, SCZ and BPD) and two distinct brain regions: BA9-prefrontal cortex (Controls (n = 6), SCZ (n = 6) and BPD (n = 6)) and hippocampus (Controls (n = 5), SCZ (n = 6) and BPD (n = 6)). In BA9, the ratio of the NRG1 N-terminal fragment relative to full length was significantly upregulated in the SCZ cohort (Bonferroni test, p = 0.011). ADAM17 was negatively correlated with full length NRG1 levels in the SCZ cohort (r = –0.926, p = 0.008). In the hippocampus we found significantly lower levels of a soluble 50 kDa NRG1 fragment in the two affected groups compared the control cohort (Bonferroni test, p = 0.0018). We also examined the relationship of specific symptomatology criteria with measures of NRG1 cleavage using the Bipolar Inventory of Signs and Symptoms Scale (BISS) and the Montgomery Åsberg Depression Rating Scale (MADRS). Our results showed a positive correlation between ADAM19 and psychosis (r = 0.595 p = 0.019); PS1 and mania (r = 0.535, p = 0.040); PS1 and depression (r = 0.567, p = 0.027) in BA9, and BACE1 with anxiety (r = 0.608, p = 0.03) in the hippocampus. Our preliminary findings suggest region-specific alterations in NRG1 cleavage in SCZ and BPD patients. These changes may be associated with specific symptoms in these psychiatric disorders.
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影响因子：
4.5
作者：
Holmes, AJ;MacDonald, A;Cohen, JD
通讯作者：
Cohen, JD
DOI：
10.1073/pnas.0800507105
发表时间：
2008-07-15
影响因子：
11.1
作者：
Dejaegere, T.;Serneels, L.;De Strooper, B.
通讯作者：
De Strooper, B.
影响因子：
4.5
作者：
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通讯作者：
Weickert, Cynthia Shannon
影响因子：
6.7
作者：
Bowden, C. L.;Singh, V.;Chang, X.
通讯作者：
Chang, X.
影响因子：
4.7
作者：
Koike, Shinsuke;Takizawa, Ryu;Kasai, Kiyoto
通讯作者：
Kasai, Kiyoto