Cell and receptor type-specific alterations in markers of GABA neurotransmission in the prefrontal cortex of subjects with schizophrenia.
Cell and receptor type-specific alterations in markers of GABA neurotransmission in the prefrontal cortex of subjects with schizophrenia.
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DOI：
10.1007/bf03033813
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发表时间：
2008-10
影响因子：
3.7
通讯作者：
Morris, Harvey M.
中科院分区：
文献类型：
--
作者：
Lewis, David A.;Hashimoto, Takanori;Morris, Harvey M.
认知控制受损，例如与工作记忆有关的认知控制受损，与精神分裂症患者的背外侧前额叶皮层（DLPFC）功能障碍有关。这种功能障碍似乎至少部分是由 GABA 介导的神经传递异常引起的。在本文中，我们回顾了最近的研究结果，表明精神分裂症患者 DLPFC 回路的改变反映了编码 GABA 神经传递选择性突触前和突触后成分的基因表达的变化。具体来说，通过综合使用多种方法，我们发现精神分裂症患者的 GABA 相关转录本表现出表达缺陷，这些转录本编码 GABA 神经传递的突触前调节因子、GABA 神经元特定亚群的神经肽标记物以及 GABAA 受体的某些亚基。特别是，神经肽生长抑素表达的改变表明，针对锥体细胞树突的 GABA 神经元 Martinotti 亚群中的 GABA 神经传递受损。相比之下，迄今为止评估的 GABA 相关转录本在长期接触抗精神病药物的猴子的 DLPFC 中没有发生改变，这表明在人类研究中观察到的效果反映了疾病的过程，而不是其治疗。与之前的研究结果一致，这些数据表明精神分裂症的工作记忆功能障碍可能归因于特定 DLPFC 微电路中 GABA 神经传递的改变。
Impairments in cognitive control, such as those involved in working memory, are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) in individuals with schizophrenia. This dysfunction appears to result, at least in part, from abnormalities in GABA-mediated neurotransmission. In this paper, we review recent findings indicating that the altered DLPFC circuitry in subjects with schizophrenia reflects changes in the expression of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission. Specifically, using a combination of methods, we found that subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding presynaptic regulators of GABA neurotransmission, neuropeptide markers of specific subpopulations of GABA neurons, and certain subunits of the GABAA receptor. In particular, alterations in the expression of the neuropeptide somatostatin suggested that GABA neurotransmission is impaired in the Martinotti subset of GABA neurons that target the dendrites of pyramidal cells. In contrast, none of the GABA-related transcripts assessed to date were altered in the DLPFC of monkeys chronically exposed to antipsychotic medications, suggesting that the effects observed in the human studies reflect the disease process and not its treatment. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia may be attributable to altered GABA neurotransmission in specific DLPFC microcircuits.