Hippocampal complexin proteins and cognitive dysfunction in schizophrenia
Hippocampal complexin proteins and cognitive dysfunction in schizophrenia
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DOI：
10.1001/archpsyc.62.3.263
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发表时间：
2005-03-01
影响因子：
--
通讯作者：
Honer, WG
中科院分区：
文献类型：
--
作者：
Sawada, K;Barr, AM;Honer, WG
背景：越来越多的神经成像和尸检证据表明，精神分裂症患者的突触末端异常。一种推测的分子机制暗示了突触前分泌机制中涉及的蛋白质异常，包括调节蛋白络合蛋白I和络合蛋白II。目的：测定精神分裂症患者海马复合体蛋白的数量和分布，并与兴奋性和抑制性神经末梢标志物平行。对功能影响也进行了研究。设计：采用免疫细胞化学方法研究海马组织中的络合素I和络合素II蛋白，以及γ -氨基丁酸（GABA）和谷氨酸的囊泡转运体。免疫细胞化学结果与通过病历回顾评估的认知功能相关。为了进一步探索人类发现的意义，我们研究了暴露于氟哌啶醇、安非他明和氯胺酮的大鼠以及接受记忆任务训练的大鼠。研究对象：我们研究了12名精神分裂症患者和12名没有已知神经精神障碍的患者的海马切片。结果：精神分裂症患者海马突触前蛋白络合蛋白ii -络合蛋白I的绝对值和比值较低。精神分裂症患者的复合体蛋白紊乱比囊泡γ -氨基丁酸或囊泡谷氨酸转运蛋白紊乱更严重。精神分裂症患者海马若干亚区络合蛋白ii -络合蛋白I比值较低与死前认知障碍严重程度呈负相关。相比之下，接受记忆训练的大鼠海马复合体ii与复合体I的比值高于未接受记忆训练的大鼠。大鼠用抗精神病药物或用拟精神药物安非他明或氯胺酮治疗没有改变络合蛋白ii与络合蛋白I的比值。结论：海马复合体蛋白的病理可能在精神分裂症中起重要作用，特别是在认知障碍方面。
Background: Converging neurointaging and postmortem evidence indicates synaptic terminals are abnormal in schizophrenia. A putative molecular mechanism implicates abnormalities of proteins involved in the presynaptic secretory machinery, including the modulator proteins complexin I and complexin II.Objectives: To determine the amount and distribution of complexin proteins in the hippocampus of subjects with schizophrenia, in parallel with markers for excitatory and inhibitory nerve terminals. The functional implications were also investigated.Design: We used immunocytochemistry to study complexin I and complexin II proteins in hippocampus, as well as the vesicular transporters for gamma-aminobutyric acid (GABA) and for glutamate. Immunocytochemical findings were correlated with cognitive function assessed through medical record review. To further explore the implications of the human findings, we studied rats exposed to haloperidol, amphetamine, and ketamine as well as rats trained in memory tasks.Subjects: We studied hippocampal sections from 12 sub-jects with schizophrenia and 12 subjects with no known neuropsychiatric disorder.Results: The absolute values and ratio of the hippocampal presynaptic proteins complexin II-complexin I were lower in subjects with schizophrenia. Disturbances in the complexin proteins in subjects with schizophrenia were greater than those observed for vesicular gamma-aminobutyric acid or vesicular glutamate transporters. The lower complexin II-complexin I ratio in several hippocampal subfields in subjects with schizophrenia was inversely correlated with the severity of antemortem cognitive impairment. In contrast, the hippocampal complexin II-complexin I ratio was higher in rats trained in a memory task compared with untrained rats. Treatment of rats with antipsychotic drugs or with the psychotomimetic drugs amphetamine or ketamine did not alter the complexin II-complexin I ratio.Conclusions: The pathology of hippocampal complexin proteins might play an important role in schizophrenia, especially concerning cognitive disturbances.