BIOT 232 |
| Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by various pathophysiological (e.g. production of amyloid &beta protein and hyperphosphorylation of tau protein) and metabolic (e.g. glucose hypometabolism) abnormalities. Epidemiological studies suggest that high fat diet significantly increases the risk of AD and the degree of saturation of fatty acids is critical in determining the risk for AD. In this context, we have previously shown that saturated free fatty acids (FFAs), palmitic acid (PA) and stearic acid (SA), had no direct effect on primary rat cortical neurons, but through astroglial metabolism these fatty acids induced increased &beta-amyloidogenesis and tau hyperphosphorylation in rat cortical neurons. These data suggested the involvement of astrocytes in mediating the FFA-induced, AD-specific effects observed in neurons and thus, further warranted a more comprehensive analysis of astroglial FFA metabolism and their role in causing AD-specific changes in neurons. In this regard, we applied metabolic flux analysis (MFA) as a tool here to gain a comprehensive insight into the metabolic profile of primary cortical astroglia in the presence of saturated FFAs. This analysis may help to identify i) the metabolic pathways involved in inducing the observed AD-specific phenotypes in the neurons and ii) potentially novel targets for therapeutic intervention in AD. Our preliminary results showed that glucose metabolism was significantly reduced in astroglia treated with pathological concentrations of PA as compared to untreated ones, thus suggesting involvement of FFAs in causing the metabolic changes in addition to the pathophysiological changes associated with AD. Study is underway to further investigate the effects of PA on other metabolic pathways in astroglia (e.g. abnormal lipid synthesis) that may contribute to development of the AD-related phenotypes. The pathways identified by the MFA are being further evaluated for their role in causing these AD-associated changes through various pharmacological and/or molecular biological means. |
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Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biochemical Technology |