Elevation of cortical C26:0 due to the decline of peroxisomal β-oxidation potentiates amyloid β generation and spatial memory deficits via oxidative stress in diabetic rats. (19th February 2016)

• Record Type: Journal Article
• Authors: Shi, Y.; Sun, X.; Sun, Y.; Hou, L.; Yao, M.; Lian, K.; Li, J.; Lu, X.; Jiang, L.
• Is Part Of: Neuroscience. Volume 315(2016)
• Page Start: 125
• Page End: 135
• Publication Date: 2016-02-19
• Subjects: ACOX1 acyl-CoA oxidase 1 -- AD Alzheimer's disease -- Aβ β-amyloid peptide -- AβPP amyloid β precursor protein -- BACE1 β-secretase -- DBP D-bifunctional protein -- DM diabetes mellitus -- DHA docosahexenoic acid -- ELOVLs elongase of very long chain fatty acids -- EPA eicosapentenoic acid -- HO-1 heme oxygenase 1 -- HD high-fat diet -- IOD integrate optical density -- MDA malondialdehyde -- MWM Morris water maze -- NOX4 NADPH oxidase 4 -- ND normal pellet diet -- PBS phosphate-buffered saline -- STZ streptozotocin -- TBA thiobarbituric acid -- THL 3-ketoacyl-CoA thiolase -- VLCFA very long chain fatty acid; type 2 diabetes mellitus -- Alzheimer's disease -- very long chain fatty acid -- peroxisomal β-oxidation -- oxidative stress; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.11.067
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Decreased peroxisomal β-oxidation and increased C26:0 were found in diabetic brain. C26:0 was positively correlated with Aβ and MDA respectively in diabetic brain. Impaired peroxisomal β-oxidation may contribute to AD progression in diabetic rats. Abstract: Diabetes mellitus correlates with subsequent development of Alzheimer's disease (AD). An accumulation of very long chain fatty acids (VLCFAs) was observed in AD brains. We found previously that inhibiting peroxisomal β-oxidation by an inhibitor caused increases in VLCFA and β-amyloid peptide (Aβ) in the cortex and primary cultured neurons of rats. Therefore, we investigated whether there was an impaired peroxisomal β-oxidation and elevated VLCFA related to the increased Aβ in the diabetic brain. This study was conducted in a type 2 diabetic rat model induced by a high-fat diet and low-dose streptozotocin. A decrease in peroxisomal β-oxidation activity caused by down-regulated thiolase expression and a consequent increase in C26:0 were observed. Meanwhile, decreases in eicosapentenoic acid (EPA) and increases in oxidative stress [indicated by levels of malondialdehyde (MDA), and the protein expression of NOX4, p47 phox and HO-1], Aβ, and the expression of AβPP and BACE1, two proteins involved in Aβ production, were observed. C26:0 levels were positively correlated with Aβ and MDA. This work suggests that in addition to decreases in EPA, increases in C26:0 by impaired peroxisomal β-oxidation can be a potential risk factor contributing to the progression of AD in diabetic brains via inducing oxidative stress.