| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
In our previous study, elderly patients with leprosy have a low prevalence of senile dementia of Alzheimer type. In addition, the frequency of B-amyloid protein deposition was lower, and hippocampal neurons were well preserved in the brain of non-demented patients with leprosy than in controls. In the present study, we examined the levels of Alzheimer's disease-related genes (B-amyloid precursor protein, presenilin-1,-2,apolipoprotein E, tau), neurotrofic factors and cytokines (NGF,GDNF,CNTF,BDNF,IGF-1,NT-3,TGF-ss,IL-2,IL-6,IL-12), proinflammatory cytokines (TNF-a,IFN-?,IL-1a/ss) and C-C chemokines (MCP-1,RANTES) mRNA by reverse transcription-competitive PCR in human neural cell lines (SK-N-SH,IMR-32) following infection with Mycobacterium leprae. The constitutive expression of every kind of Alzheimer's disease-related genes, and CNTF,BDNF,IGF-1,NT-3,IL-12,TNF-a,IL-1a/ss,RANTES mRNA was identified in these cell lines. The levels of Alzheimer's disease-related genes mRNA were unaltered in IMR-32 cell lines following exposure to lysate of Mycobacterium leprae, whereas PS-2 mRNA expression was upregulated in SK-N-SH cells after this treatment. The levels of RANTES mRNA was also upregulated in both cell lines after this treatment. These results indicate that the existence of cell specific mechanisms and/or different regulatory system for the expression of PS-1,2 genes in human neural cells. These finding is also speculated that Mycobacterium leprae-infected human neural cells produce C-C chemokine RANTES, its induce focal inflammatory with resulting nerve damage in central nervous system. Further work is in progress to clear the significance of expression of Alzheimer's disease-related genes in human neural cells following infection with Mycobacterium leprae.
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