An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer's disease.
An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer's disease.
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DOI：
10.1111/j.1440-1789.2010.01193.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Asada T
中科院分区：
文献类型：
--
作者：
Mizukami K;Ishikawa M;Akatsu H;Abrahamson EE;Ikonomovic MD;Asada T
阿尔茨海默病 (AD) 与神经元变性、突触丧失和多种神经递质系统缺陷有关。血清素 1A (5-HT1A) 受体的改变可能会导致 AD 认知功能受损，体外结合和 PET 成像研究均表明海马/内侧颞叶皮质中的 5-HT1A 受体在 AD 早期受到影响。这项神经病理学研究检查了 AD 海马中 5-HT1A 受体蛋白的定位和免疫反应强度，目的是确定神经元受体水平是否受到 Braaks 病理分期定义的神经原纤维缠结 (NFT) 严重程度的影响，并为结合测定和 PET 成像研究提供免疫组织化学确认。受试者包括 AD 患者和非 AD 对照 (NC)，分为三个 Braaks 阶段（Braak 0–II，NC；Braak III/IV 和 V/VI，AD）。在 Braak 0–II 组中，5-HT1A 免疫反应性 (ir) 在 CA1 和下托神经毡中显着，在齿状回分子层 (DGml) 中中等，在 CA3 和 CA4 中较低。 Braak III/IV 组的 AD 受试者海马中未观察到 5-HT1A-ir 变化。 Braak V/VI 组 11 名受试者中有 6 名 (54.5%) 的 CA1 区海马 5-HT1A-ir 强度显着降低。在所有三组中，5HT1A-ir 减少与 CA1 中的神经元损失之间存在统计学上显着的关联，但在 CA3 中则没有。目前的数据表明，海马 5-HT1A 受体主要保留到 AD 的 NFT 进展末期。因此，使用 5-HT1A 特异性放射性标记探针作为海马神经元损失标记的 PET 成像的效用可能仅限于晚期 AD 病例的 CA1 区域。
Alzheimer’s disease (AD) is associated with neuronal degeneration, synaptic loss, and deficits in multiple neurotransmitter systems. Alterations in the serotonin 1A (5-HT1A) receptor can contribute to impaired cognitive function in AD, and both in vitro binding and PET imaging studies have demonstrated that 5-HT1A receptors in the hippocampus/medial temporal cortex are affected early in AD. This neuropathological study examined the localization and immunoreaction intensity of 5-HT1A receptor protein in AD hippocampus with the goal to determine whether neuronal receptor levels are influenced by the severity of neurofibrillary tangles (NFT) severity defined by Braaks’ pathological staging and to provide immunohistochemical confirmation of the binding assays and PET imaging studies. Subjects included AD patients and non-AD controls (NC) stratified into three Braaks’ stages (Braak 0–II, NC; Braak III/IV and V/VI, AD). In the Braak 0–II group, 5-HT1A-immunoreactivity (ir) was prominent in the neuropil of the CA1 and subiculum, moderate in the dentate gyrus molecular layer (DGml), and low in the CA3 and CA4. No changes in 5-HT1A-ir were observed in the hippocampus of AD subjects in the Braak III/IV group. Hippocampal 5-HT1A-ir intensity was markedly decreased in the CA1 region in 6 out of 11 (54.5%) subjects in the Braak V/VI group. Across all three groups combined, there was a statistically significant association between reduced 5HT1A-ir and neuronal loss in the CA1, but not in the CA3. The present data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until the end-stage of NFT progression in AD. Thus, the utility of PET imaging using a 5-HT1A specific radiolabeled probe as a marker of hippocampal neuronal loss may be limited to the CA1 field in advanced stage AD cases.
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影响因子：
2.9
作者：
Aznar, S;Qian, ZX;Knudsen, GM
通讯作者：
Knudsen, GM
影响因子：
6.6
作者：
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DOI：
10.1073/pnas.97.26.14731
发表时间：
2000-12-19
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作者：
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