Inorganic biochemical investigation in diffuse neurofibrillary tangles with calcification

弥漫性神经原纤维缠结钙化的无机生化研究

• 批准号: 14570916
• 负责人: TAKEUCHI Tohru
• 金额: $ 1.66万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570916/
• 关键词: DNTC; SRXRF; lead; calcium; calcification; 石灰沈着; 生体無機化学; SRXRF分析

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

DNTC的特征在于阿尔茨海默病（AD）和皮克病（PD）中重叠的临床症状和神经病理学发现，以及明显的钙质沉积。本研究用DNTC法研究了尸体脑组织中钙沉积与其它金属元素的关系。对照组为AD和非老年性神经退行性变脑组织。分别用EPMA-EDX光谱（JSM-T220装备的JEOL jed-2001）和同步辐射荧光光谱（SRXRF）分析额叶、颞叶和枕叶皮质。测量条件如下：加速电压，20 kV;束流，10 μA ; EPMA-EDX中测量时间，100秒;储存环中电子束能量，2.5GeV;最大电流，400 mA ; SRXRF中入射X射线能量，14.9keV。对于EPMA-EDX分析，使用-80℃冷冻切片。对于SRXRF分析，用4%多聚甲醛固定的石蜡切片和-80℃冻存的样品， ...更多信息 在SRXRF分析中，从DNTC大脑额叶和颞叶皮质的血管钙化区检测到高浓度的金属元素，如铅（Pb）、汞、锌和钙。石蜡包埋的额叶皮质SRXRF成像和染色照片显示，Pb集中在血管周围，与Ca一致。这一结果表明，血管中高水平的Ca和Pb可能导致钙化，并且这些元素可以从血液中渗入神经元。在对照脑组织中没有检测到高浓度的这些元素。铅是中枢神经系统中一种主要的假定神经毒性物质，也是研究得最多的神经毒素。铅是一种对蛋白质上的巯基具有特殊亲和力的反应性二价阳离子.其潜在的毒性作用有：（1）干扰线粒体结构和功能，（2）与其他二价阳离子竞争结合位点，（3）干扰膜功能，（4）抑制酶活性，（5）增加血管通透性等。铅在脑内的蓄积有可能促进DNTC的进展。少

项目成果

R.Ishihara, T.Kawakami, Y.Mizuno, T.Takeuchi, A.I.Ektessabi: "Neuronal degeneration from the perspective of abnormal distribution of cellular metallic elements in cases of Alzheimer's disease"Biomedical research on trace elements, suppl.Ohsaka. 14(2). 107

R.Ishihara、T.Kawakami、Y.Mizuno、T.Takeuchi、A.I.Ektessabi：“从阿尔茨海默病病例中细胞金属元素异常分布的角度来看神经变性”微量元素生物医学研究，增刊Ohsaka。

N.Hashimoto, T.Takeuchi, R.Ishihara, K.Ukai et al.: "Gilial fibrillary tangles in diffuse neurofibrillary tangles with calcificatrion"Acta Neuropatholol. 106. 150-156 (2003)

N.Hashimoto、T.Takeuchi、R​​.Ishihara、K.Ukai 等人：“伴有钙化的弥漫性神经原纤维缠结中的胶质原纤维缠结”Acta Neuropatholol。

N Hashimoto, T Takeuchi, R Ishihara, K Ukai, H Kobayashi, Hiromu Iwata, K Iwai, Y Mizuno, H Yamaguchi, Hiroto Shibayama: "Glial fibrillary tangles in diffiuse neurofibrillary tangles with calcificatrion."Acta Neuropatholol. 106. 150-156 (2003)

N Hashimoto、T Takeuchi、R​​ Ishihara、K Ukai、H Kobayashi、Hiromu Iwata、K Iwai、Y Mizuno、H Yamaguchi、Hiroto Shibayama：“伴有钙化的弥漫性神经原纤维缠结中的胶质纤维缠结。”神经病理学报。

K.Ishihara, A.I.Ektessabi, T.Kawakami, Y.Mizuno, T.Takeuchi: "Investigation on metal elements in the brain tissues from DNTC patients"9th International conference on electronic spectroscopy & structure, abs, Sweden. 244-244 (2003)

K.Ishihara、A.I.Ektessabi、T.Kawakami、Y.Mizuno、T.Takeuchi：“DNTC 患者脑组织中金属元素的调查”第九届国际电子光谱会议

N Hashimoto, T.Takeuchi, R.Ishihara, K.Ukai et al.: "Glial fibrillary tangles in diffuse neurofibrillary tangles with calcificatrion."Acta Neuropatholol. 106. 150-156 (2003)

N Hashimoto、T.Takeuchi、R​​.Ishihara、K.Ukai 等人：“伴有钙化的弥漫性神经原纤维缠结中的胶质原纤维缠结。”Acta Neuropatholol。