| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
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
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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
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