Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease
Open Access
- 4 June 2008
- journal article
- Published by Springer Science and Business Media LLC in BMC Research Notes
- Vol. 1 (1), 20
- https://doi.org/10.1186/1756-0500-1-20
Abstract
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.Keywords
This publication has 25 references indexed in Scilit:
- Involvement of astroglial ceramide in palmitic acid‐induced Alzheimer‐like changes in primary neuronsEuropean Journal of Neuroscience, 2007
- Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neuronsNeuroscience Letters, 2006
- Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic miceNeurobiology of Disease, 2006
- Pathways towards and away from Alzheimer's diseaseNature, 2004
- The Acyl-CoA Synthetase “Bubblegum” (Lipidosin)Published by Elsevier BV ,2003
- De novo‐synthesized ceramide signals apoptosis in astrocytes via extracellular signal‐regulated kinaseThe FASEB Journal, 2000
- 15-year longitudinal study of blood pressure and dementiaThe Lancet, 1996
- Okadaic Acid Increases Nerve Growth Factor Secretion, mRNA Stability, and Gene Transcription in Primary Cultures of Cortical AstrocytesPublished by Elsevier BV ,1995
- Chronic Ethanol Exposure Potentiates NMDA Excitotoxicity in Cerebral Cortical NeuronsJournal of Neurochemistry, 1993
- Regional and Subcellular Distribution of ATP‐Citrate Lyase and Other Enzymes of Acetyl‐CoA Metabolism in Rat BrainJournal of Neurochemistry, 1980