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Age-associated changes in synaptic lipid raft proteins revealed by two-dimensional fluorescence difference gel electrophoresis
Jiang, Lei Fang, Jianwen Moore, David S. Gogichaeva, Natalia V. Galeva, Nadezhda A. Michaelis, Mary Lou Zaidi, Asma
Jiang, Lei
Fang, Jianwen
Moore, David S.
Gogichaeva, Natalia V.
Galeva, Nadezhda A.
Michaelis, Mary Lou
Zaidi, Asma
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Abstract
Brain aging is associated with a progressive decline in cognitive function though the molecular mechanisms remain unknown. Functional changes in brain neurons could be due to age-related alterations in levels of specific proteins critical for information processing. Specialized membrane microdomains known as ‘lipid rafts’ contain protein complexes involved in many signal transduction processes. This study was undertaken to determine if two-dimensional fluorescence difference gel electrophoresis (2D DIGE) analysis of proteins in synaptic membrane lipid rafts revealed age-dependent alterations in levels of raft proteins. Five pairs of young and aged rat synaptic membrane rafts were subjected to DIGE separation, followed by image analysis and identification of significantly altered proteins. Of 1046 matched spots on DIGE gels, 94 showed statistically significant differences in levels between old and young rafts, and 87 of these were decreased in aged rafts. The 41 most significantly altered (p < 0.03) proteins included several synaptic proteins involved in energy metabolism, redox homeostasis, and cytoskeletal structure. This may indicate a disruption in bioenergetic balance and redox homeostasis in synaptic rafts with brain aging. Differential levels of representative identified proteins were confirmed by immunoblot analysis. Our findings provide novel pathways in investigations of mechanisms that may contribute to altered neuronal function in aging brain.
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Date
2008-12-31
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Elsevier
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Keywords
2D DIGE, Brain aging, Energy metabolism, Lipid rafts, Synaptic dysfunction
Citation
Jiang, Lei et al. “Age-Associated Changes in Synaptic Lipid Raft Proteins Revealed by Two-Dimensional Fluorescence Difference Gel Electrophoresis.” Neurobiology of aging 31.12 (2010): 2146–2159.