Law Amanda J, Weickert Cynthia Shannon, Hyde Thomas M, Kleinman Joel E, Harrison Paul J
University Department of Psychiatry, Neurosciences Building, Warneford Hospital, Oxford OX3 7JX, UK.
Am J Psychiatry. 2004 Oct;161(10):1848-55. doi: 10.1176/ajp.161.10.1848.
Aberrant synaptic connectivity may underlie the involvement of the hippocampus in schizophrenia. There is reasonable neuropathological evidence for a presynaptic pathology but few studies of the postsynaptic component. This study tested the hypothesis that hippocampal dendritic pathology is also present in schizophrenia.
Using in situ hybridization in sections of hippocampal formation from 10 patients with schizophrenia, 10 patients with mood disorders (three with bipolar disorder and seven with major depression), and 10 healthy comparison subjects, the authors examined the expression of two important dendritic genes: spinophilin, which serves as a marker of dendritic spines, and microtubule-associated protein 2 (MAP2), an overall dendritic marker.
The patients with schizophrenia had lower levels of spinophilin mRNA in CA4 (hilus), CA3, the subiculum, and the entorhinal cortex than did the normal comparison subjects. The mood disorder group showed similar differences from the comparison group. MAP2 and cyclophilin mRNA did not differ between the groups in any subfield.
Decreased spinophilin but unchanged MAP2 expression provides molecular evidence for a hippocampal dendritic pathology in schizophrenia that preferentially affects the spines. As spines are the target of most glutamatergic synapses, the data extend the evidence that excitatory synapses are particularly affected. Similar dendritic spine pathology may also occur in mood disorders.
异常的突触连接可能是海马体参与精神分裂症发病的基础。有合理的神经病理学证据支持存在突触前病变，但对突触后成分的研究较少。本研究检验了精神分裂症患者海马体树突也存在病变这一假设。
作者利用原位杂交技术，对10例精神分裂症患者、10例情绪障碍患者（3例双相情感障碍患者和7例重度抑郁症患者）以及10名健康对照者的海马结构切片进行检测，观察两个重要树突基因的表达情况：作为树突棘标志物的亲嗜素，以及作为整体树突标志物的微管相关蛋白2（MAP2）。
精神分裂症患者CA4区（海马齿状回）、CA3区、海马下脚和内嗅皮质中的亲嗜素mRNA水平低于正常对照者。情绪障碍组与对照组也表现出类似差异。各亚区中，MAP2和亲环蛋白mRNA在各组间无差异。
亲嗜素表达降低但MAP2表达无变化，为精神分裂症患者海马体树突病变提供了分子证据，且这种病变优先影响树突棘。由于树突棘是大多数谷氨酸能突触的靶点，这些数据进一步证明兴奋性突触受到了特别影响。类似的树突棘病变也可能发生在情绪障碍中。
