| Summary: | 碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 92 === In recent year, many evidences revealed that the lesion of Alzheimer’s disease (AD) is in a chronic cerebral inflammation. The extracellular deposits of beta-amyloid (Aβ), which aggregate in the brain of AD as a component of the neuritic plaque（or senile plaque）, bring about neuronal damage and microglial activation. Aβ has the ability to activate cells of neuronal system, makes it to release some substrate either leading inflammation or being a toxicant, which bring about inflammation and generate the death of neuronal cells. In this study, we established the cell culture model that to investigate the effect about the factor happening on inflammation to neuronal cells, which about the cell survival, signal transduction and functional effect.
Stimulation of different kind of NO (nitric oxide) redox forms with different dose (including SNP (NO＋), SNAP (NO•), Sin-1 (NO• and O2－) and Angeli’s salt (NO−)) to SK-N-SH，activate ERK、JNK、p38MAPK and caspase also induce apoptosis. The responses between the stimulation of different kinds of NO redox form are quite similar. There are some reasons including the effect with different kinds of NO redox form and the different NO releasing kinetics of these NO donors. These result suggest Aβ□□□□□ could not induce the M-CSF (macrophage-colony stimulating factor) expression of SK-N-SH but NO could. LPS (Lipopolysaccharide) could induce M-CSF expression significantly in a dose –dependent manner. But we could not find the same expression on Neuro-2a and IMR-32, maybe it just the specific response on SK-N-SH. Pre-treat of PXB (polymyxin B) could not inhibit the effect of LPS, and the detoxified LPS would not induce M-CSF, which means perhaps LPS works through the unknown receptor and signal transduction to make the response of SK-N-SH. We have found that to inhibit α-secretase and γ-secretase would reduce the production of sAPPα and Aβ□□□□□□□ by treat IMR-32 satble clone and wild-type with SNP. By pre-treat with inhibitor and try to find out the pathway of α-secretase, reveal that MAPKs and Akt/PI3K does not involve. We suppose that should be the specific effect of NO to inhibit the releasing of Aβ□□□□□□ because of KFC and H2O2. SNP activate GSK-3α/β, LiCl increase the releasing of Aβ□□□□ and LY294002 reduce it which all means that NO may through the activation of GSK-3β and/or Akt to inhibit Aβ□□□□□
Depanding on those evidence, the NO, secreted by microglial cell on the chronic cerebral inflammation of AD patients, lead to MAPK singal transduction, the activation of caspase and apoptosis and also regulate M-CSF. The production of Aβ which is one reason of AD arise also has inhibited by NO. This shows NO play a important role in physiological and pathological condition in AD.
|
|---|
