探討DHA抵抗類澱粉蛋白誘發之神經毒性以預防阿茲海默氏病之機轉

王寶源

doi:10.6342/NTU.2006.02099

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探討DHA抵抗類澱粉蛋白誘發之神經毒性以預防阿茲海默氏病之機轉

Mechanism of DHA against β-amyloid induced neurotoxicity studied in primary hippocampal cells

王寶源 , Masters　　Advisor：蘇慧敏　　

繁體中文 DOI： 10.6342/NTU.2006.02099

阿茲海默氏病；類澱粉蛋白；微小管；微管；海馬回；二十二碳六烯酸； β-amyloid ； Aβ ； microtubule ； microfilament ； hippocampus ； Docosahexaenoid acid ； DHA

Abstract │ Reference (140) │ Altmetrics

Abstract 〈TOP〉

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Alzheimer’s disease (AD) is a progressing neurodegenerative disease characterized by dementia to a degree that it infers with person’s ability and function. The aim of the study is to understand the mechanism of docosahexaenoic acid (DHA, 22:6ω3) on the progression of AD by conducting studies in primary hippocampal cells supplemented with 0~50 uM DHA. We hypothesized that increased DHA level in membrane structure of hippocampal neuron would build up a barrier to against neurotoxicity induced by fibrillar amyloid b peptide (Ab42), and increased microtubules dynamics.

It was found that: 
（1）The optimal concentration of DHA for the survival of cultiured primary hippocampal cells was 10μM.
（2）The DHA supplemented to the medium did increase the DHA level in hippocampal cells as a dose-dependent level.
（3）The increased DHA level in hippocampal cells did against neurotoxicity induced by fibrillar Ab42 to increase its cell viability.
（4）The 5uM but not 25uM DHA supplemented to medium did increase 61% tyrosinated tubulin expression, a maker of dynamic microtubules, compare with controls. 
（5）The 25uM but not 5uM DHA supplemented to medium did upregulate 9% acetylated tubulin expression, a maker of stabilized microtubules, compared with controls.  
（6）The 25uM but not 5uM DHA supplemented to medium did downregulate 37%β-actin compared with controls.
We concluded that the supplemented DHA can be incorporated into the hippocampal cells to increase its survival, did against Aβ42 induced neurotoxicity and regulate microtubule dynamics, suggesting DHA is a potential supplement for AD prevention.

Reference ( 140 ) 〈TOP〉

AHMAD A, MORIGUCHI T & SALEM N. (2002). Decrease in neuron size in docosahexaenoic acid-deficient brain. Pediatr Neurol 26, 210-218.
連結：
AKBAR M & KIM HY. (2002). Protective effects of docosahexaenoic acid in staurosporine-induced apoptosis: involvement of phosphatidylinositol-3 kinase pathway. J Neurochem 82, 655-665.
連結：
AKSENOV MY, AKSENOVA MV, BUTTERFIELD DA, GEDDES JW & MARKESBERY WR. (2001). Protein oxidation in the brain in Alzheimer's disease. Neuroscience 103, 373-383.
連結：
AKSENOVA MV, AKSENOV MY, PAYNE RM, TROJANOWSKI JQ, SCHMIDT ML, CARNEY JM, BUTTERFIELD DA & MARKESBERY WR. (1999). Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders. Dement Geriatr Cogn Disord 10, 158-165.
連結：
ALBERTS B, JOHNSON A, LEWIS J, RAFF M, ROBERTS K & WALTER P. (2002). molecular biology of the cell.
連結：

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