Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease

被引：22
作者：
Patil S. [1 ]
Balu D. [1 ]
Melrose J. [1 ]
Chan C. [1 ,2 ]
机构：
[1] Department of Chemical Engineering and Material Science, Michigan State University, East Lansing, MI
[2] Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI
来源：
BMC Research Notes | / 1卷 / 1期
基金：
美国国家科学基金会; 美国国家卫生研究院;
关键词：
Cortical Neuron; Ceramide Synthesis; Affected Brain Region; Free Fatty Acid Metabolism; Cerebellar Medium;
D O I：
10.1186/1756-0500-1-20
中图分类号：
学科分类号：
摘要：
Background. Alzheimer's disease (AD) is a progressive, neurodegenerative disease mostly affecting the basal forebrain, cortex and hippocampus whereas the cerebellum is relatively spared. The reason behind this region-specific brain damage in AD is not well understood. Here, we report our data suggesting "differential free fatty acid metabolism in the different brain areas" as a potentially important factor in causing the region-specific damage observed in AD brain. Findings. The astroglia from two different rat brain regions, cortex (region affected in AD) and cerebellum (unaffected region), were treated with 0.2 mM of palmitic acid. The conditioned media were then transferred to the cortical neurons to study the possible effects on the two main, AD-associated protein abnormalities, viz. BACE1 upregulation and hyperphosphorylation of tau. The conditioned media from palmitic-acid treated cortical astroglia, but not the cerebellar astroglia, significantly elevated levels of phosphorylated tau and BACE1 in cortical neurons as compared to controls (47 7% and 45 4%, respectively). Conclusion. The present data provide an experimental explanation for the region-specific damage observed in AD brain; higher fatty acid-metabolizing capacity of cortical astroglia as compared to cerebellar astroglia, may play a causal role in increasing vulnerability of cortex in AD, while sparing cerebellum. © 2008 Patil et al; licensee BioMed Central Ltd.
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共 25 条
[1]  
Mattson M.P., Pathways towards and away from Alzheimer's disease, Nature, 430, 7000, pp. 631-639, (2004)
[2]  
Cunha-Oliveira T., Rego A.C., Cardoso S.M., Borges F., Swerdlow R.H., MacEdo T., De Oliveira C.R., Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine, Brain Res, 1089, 1, pp. 44-54, (2006)
[3]  
Lee M.S., Kwon Y.T., Li M., Peng J., Friedlander R.M., Tsai L.H., Neurotoxicity induces cleavage of p35 to p25 by calpain, Nature, 405, 6784, pp. 360-364, (2000)
[4]  
Grant W.B., Dietary links to Alzheimer's disease: 1999 update, J Alzheimers Dis, 1, 4-5, pp. 197-201, (1999)
[5]  
Levin-Allerhand J.A., Lominska C.E., Smith J.D., Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet, J Nutr Health Aging, 6, 5, pp. 315-319, (2002)
[6]  
Oksman M., Iivonen H., Hogyes E., Amtul Z., Penke B., Leenders I., Broersen L., Lutjohann D., Hartmann T., Tanila H., Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice, Neurobiol Dis, 23, 3, pp. 563-572, (2006)
[7]  
Skoog I., Lernfelt B., Landahl S., Palmertz B., Andreasson L.-A., Nilsson L., Persson G., Oden A., Svanborg A., 15-year longitudinal study of blood pressure and dementia, Lancet, 347, 9009, pp. 1141-1145, (1996)
[8]  
Arvanitakis Z., Wilson R.S., Bienias J.L., Evans D.A., Bennett D.A., Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function, Arch Neurol, 61, 5, pp. 661-666, (2004)
[9]  
Whitmer R.A., Gunderson E.P., Barrett-Connor E., Quesenberry Jr. C.P., Yaffe K., Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study, British Medical Journal, 330, 7504, pp. 1360-1362, (2005)
[10]  
Guo Z., Cupples L.A., Kurz A., Auerbach S.H., Volicer L., Chui H., Green R.C., Sadovnick A.D., Duara R., Decarli C., Johnson K., Go R.C., Growdon J.H., Haines J.L., Kukull W.A., Farrer L.A., Head injury and the risk of AD in the MIRAGE study, Neurology, 54, 6, pp. 1316-1323, (2000)
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