Inorganic biochemical investigation in diffuse neurofibrillary tangles with calcification

DNTC的特点是阿尔茨海默病（AD）和皮克病（PD）的临床症状和神经病理表现重叠，并伴有明显的钙质沉积。在这项研究中，我们用DNTC研究了尸检脑组织中钙（Ca）沉积与其他金属元素的关系。AD和非老年性神经退行性变脑组织作为对照。分别用EPMA-EDX光谱（JSM-T220装备JEOL jed-2001）和同步辐射荧光（SRXRF）光谱法分析额叶、颞叶和枕叶皮层。测量条件为：加速电压20kV；束流，10 μA；测量时间，EPMA-EDX为100秒；存储环中的电子束能量为2.5 GeV；最大电流400ma；SRXRF的入射x射线能量为14.9 keV。EPMA-EDX分析采用-80℃冷冻切片。SRXRF分析采用4%多聚甲醛固定石蜡切片和-80℃冷冻石蜡切片。在SRXRF分析中，在DNTC脑额叶和颞叶皮层血管钙化区检测到高浓度的铅、汞、锌和钙等金属元素。额叶皮质石蜡包埋的SRXRF成像和染色照片显示，Pb在血管周围集中，与Ca一致，提示血管中Ca和Pb的高含量可能导致钙化，这些元素可能从血液中浸润到神经元中。在对照组脑组织中没有检测到高浓度的这些元素。铅被认为是中枢神经系统中主要的神经毒性物质，也是研究得最好的神经毒素。铅是一种-活性二价阳离子，对蛋白质上的巯基具有特殊的亲和力。其潜在的毒性作用有：(1)扰乱线粒体结构和功能，(2)与其他二价阳离子竞争结合位点，(3)扰乱膜功能，(4)抑制酶活性，(5)增加血管通透性等。由于过量的铅摄入可能是脑钙化的病因之一，因此脑内铅的积累可能促进DNTC的进展。少

DNTC is characterized by overlapping clinical symptoms and neuropathological findings in Alzheimer's disease (AD) and Pick's disease (PD), and pronounced calcareous deposits. In this study, we investigated the relation between the calcium (Ca) deposits and other metallic elements in autopsy brain tissues with DNTC. Brain tissues with AD and non-senile neurodegeneration were used for the controls. The frontal, temporal, and occipital cortices were analyzed respectively by EPMA-EDX spectroscopy (JSM-T220 equipped JEOL jed-2001) and synchrotron radiation fluorescence (SRXRF) spectrometry. The measurement conditions were as follows : accelerating voltage, 20kV ; beam current, 10 μA ; measurement time, 100 sec in EPMA-EDX ; electron beam energy in the storage ring, 2.5 GeV ; maximum current, 400 mA ; and incident X-ray energy, 14.9 keV in SRXRF. For EPMA-EDX analysis, -80℃ frozen sections were used. For SRXRF analysis, both paraffin sections fixed with 4% paraformaldehyde and -80℃ frozen se … More ctions were used.In SRXRF analysis high concentrations of metallic elements such as lead (Pb), mercury, zinc and Ca were detected from the vascular calcified regions in the frontal and temporal cortices of DNTC brains. The SRXRF imaging and stained photograph of the paraffin embedded frontal cortex showed that Pb was concentrated around the blood vessels, coinciding with Ca. This result suggests that high levels of Ca and Pb in blood vessels probably lead to the calcification, and that these elements could be infiltrated into the neurons from blood. No high concentrations of these elements were detected in control brain tissues.Pb is a major putative neurotoxic substance in the central nervous system, and the best-studied neurotoxin. Pb is a -reactive divalent cation with a particular affinity for the sulfhydryl groups on proteins. Its potential toxic effects are (1) disturbance of mitochondrial structure and function, (2) competition with other divalent cations for binding sites, (3) disturbance of membrane function, (4) inhibition of enzyme activity, (5) increased vascular permeability, etc. Since the excessive Pb intake might be one of the etiological factors of calcification in the brain, Pb accumulations in the brain have the potential to promote the progression of DNTC. Less