Abstract
In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.
Highlights
In some neurodegenerative diseases, very long-chain fatty acids (VLCFA, carbon atoms > 22) are present in abnormally large quantities in many tissues and can induce lipotoxicity
Alterations in peroxisomal function are suspected of contributing in the etiology of various neurodegenerative diseases: (a) multiple sclerosis: high concentrations of C26:0 are present in grey matter as well as in serum [1,2], (b) Alzheimer’s disease: there is an accumulation of C22:0, C24:0 and C26:0 [3], (c) X-linked adrenoleukodystrophy (X-ALD): there is an accumulation of C24:0, C26:0 and C26:1, in tissue and plasma caused by mutations in the ABCD1 gene, (d) dementia: there are higher levels of C26:0 in the plasma and red blood cells [4]
The Aurora Pujol’s team tested an antioxidant cocktail: N-acetyl-cysteine, α-lipoic acid, and α-tocopherol in an X-linked adrenoleukodystrophy model [6]. This cocktail is capable of reversing the oxidative stress and locomotor impairment induced by VLCFA [6,7]
Summary
Very long-chain fatty acids (VLCFA, carbon atoms > 22) are present in abnormally large quantities in many tissues and can induce lipotoxicity. Alterations in peroxisomal function are suspected of contributing in the etiology of various neurodegenerative diseases: (a) multiple sclerosis: high concentrations of C26:0 are present in grey matter as well as in serum [1,2], (b) Alzheimer’s disease: there is an accumulation of C22:0, C24:0 (tetracosanoic acid or lignoceric acid) and C26:0 [3], (c) X-linked adrenoleukodystrophy (X-ALD): there is an accumulation of C24:0, C26:0 and C26:1, in tissue and plasma caused by mutations in the ABCD1 gene, (d) dementia: there are higher levels of C26:0 in the plasma and red blood cells [4] In these different pathologies, the central and/or peripheral nervous system is affected and undergoes demyelination. We evaluated the effect of DHA on different parameters related to cell death in 158N murine oligodendrocytes: cell viability, mitochondrial activity, membrane permeability, oxidative stress and autophagy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
