Partial loss of parvalbumin-containing hippocampal interneurons in dementia with Lewy bodies
Partial loss of parvalbumin-containing hippocampal interneurons in dementia with Lewy bodies
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DOI：
10.1111/j.1440-1789.2010.01117.x
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发表时间：
2011-02-01
期刊：
影响因子：
2.3
通讯作者：
Perry, Elaine K.
中科院分区：
文献类型：
--
作者：
Bernstein, Hans-Gert;Johnson, Mary;Perry, Elaine K.
路易体痴呆（DLB）是第二常见的神经退行性痴呆。在 DLB 的许多其他神经病理学变化中，有报道称大脑区域特异性细胞缺陷。它们包括运动神经元和锥体细胞密度的降低，而含有新皮质小白蛋白（parv）的神经元被认为不含路易体，并且在DLB中幸免。然而，在路易体痴呆患者的脑脊液中发现 parv 水平升高。我们使用针对钙结合蛋白的特异性抗体，对特征明确的 DLB 病例和对照组的海马 parv 免疫反应性神经元进行了免疫组织化学分析。此外，还对α-突触核蛋白的区域和细胞分布进行了分析。 DLB 受试者和对照组海马上小病毒免疫反应性 (ir) 神经元的亚场和层状分布仅表现为齿状回 (DG)/门的非颗粒细胞和海马 CA1、CA2、CA3 和 CA4 区域的非锥体细胞。 DLB 和对照之间的分布模式没有质的差异。 parv-ir 神经元密度的定量估计显示齿状 (DG)/门区域以及 CA1 子区域显着减少。双重免疫标记实验表明，只有 2% 表达 parv 的中间神经元充满 α-突触核蛋白免疫反应物质。 DLB 病例中总神经元密度没有发现显着变化。我们的结果显示，DLB 中表达 parv 的海马中间神经元部分丢失，这可能是长期钙超载与线粒体功能受损相结合的结果。海马中间神经元这一特定子集的数量减少是否会对 DLB 患者的伽马（20-80 Hz）频率活动产生影响，仍有待阐明。
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Among many other neuropathological changes in DLB, brain region-specific cellular deficits have been reported. They include decreases in motor neuron and pyramidal cell densities, while neocortical parvalbumin (parv)-containing neurons are thought to be free of Lewy bodies and spared in DLB. However, elevated parv levels are found in the cerebrospinal fluid of patients suffering from dementia with Lewy bodies. We performed an immunohistochemical analysis of hippocampal parv-immunoreactive neurons in well-characterised DLB cases and from controls using a specific antibody against the calcium binding protein. In addition, an analysis of the regional and cellular distribution of alpha-synuclein was carried out. Subfield and laminar distribution of parv-immunoreactive (ir) neurons on the hippocampus in subjects with DLB and controls were present exclusively as non-granule cells of the dentate gyrus (DG)/hilus and non-pyramidal cells of CA1, CA2, CA3 and CA4 areas of the hippocampus. The distribution patterns did not differ qualitatively between DLB and controls. Quantitative estimation of parv-ir neuron density revealed significant decreases in the dentate (DG)/hilus region as well as in the CA1 subfield. Double immunolabelling experiments showed that only 2% of parv expressing interneurons were laden with alpha-synuclein immunoreactive material. No significant changes were found for the total neuron densities in DLB cases. Our results show a partial loss of parv-expressing hippocampal interneurons in DLB, which might be the result of long-lasting calcium overload in combination with a proposed impaired mitochondrial function. It remains to be elucidated if the numerical decrease of this particular subset of hippocampal interneurons has consequences for the gamma (20-80 Hz) frequency activity in DLB patients.