Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs
Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs
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DOI：
10.1038/sj.mp.4000741
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发表时间：
2000-07-01
影响因子：
11
通讯作者：
Harrison, PJ
中科院分区：
文献类型：
--
作者：
Eastwood, SL;Harrison, PJ
复合蛋白 (cx) I 和 cx II 是分别由抑制性和兴奋性海马神经元优先表达的突触蛋白。我们之前报道了精神分裂症中海马结构 ex mRNA 和蛋白质表达的减少，cx II 的损失比 cx I 的损失更大。目前的原位杂交研究既是一次复制尝试，也是一项扩展到包括双相和单相情绪障碍的研究，使用的是斯坦利基金会大脑系列的切片。在精神分裂症中，这两种 mRNA 在某些海马亚区（尤其是 CA4）中均减少，但在下托中保留，cx II/cx I mRNA 比率没有变化。在双相情感障碍中，CA4、下托和海马旁回的 mRNA 减少，下托的缺陷具有诊断特异性。在重度抑郁症中没有发现 ex mRNA 的改变，用抗精神病药物（氟哌啶醇或氯丙嗪）治疗大鼠 2 周对海马 ex mRNA 没有影响。这些数据重复了精神分裂症中海马 ex I 和 ex II 表达减少的发现，并在双相情感障碍中显示出类似或更大的异常。精神分裂症中 cx II > cx I mRNA 丢失的不复制意味着兴奋性连接优先参与的假设没有得到支持。这些结果进一步证明，回路改变可能是精神分裂症和躁郁症的神经解剖学的一个组成部分。
Complexin (cx) I and cx II are synaptic proteins preferentially expressed by inhibitory and excitatory hippocampal neurons respectively. We previously reported decreased hippocampal formation ex mRNA and protein expression in schizophrenia, with a greater loss of cx II than cx I. The present in situ hybridization study was both an attempt at replication, and an extension to include bipolar and unipolar mood disorders, using sections from the Stanley Foundation brain series. In schizophrenia, both mRNAs were decreased in some hippocampal subfields, especially CA4, but were preserved in subiculum, The cx II/cx I mRNA ratio was unchanged. In bipolar disorder, the mRNAs were reduced in CA4, subiculum and parahippocampal gyrus, with the deficit in subiculum being diagnostically specific. No alterations in ex mRNAs were found in major depression, Treatment of rats with antipsychotics (haloperidol or chlorpromazine) for 2 weeks had no effect on hippocampal ex mRNAs, These data replicate the finding of decreased ex I and ex II expression in the hippocampus in schizophrenia and show a similar or greater abnormality in bipolar disorder. Non-replication of the cx II > cx I mRNA loss in schizophrenia means that the hypothesis of a preferential involvement of excitatory connections was not supported. The results extend the emerging evidence that altered circuitry may be a component of the neuroanatomy of both schizophrenia and bipolar mood disorder.