Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis
Lipid metabolism is profoundly dysregulated in amyotrophic lateral sclerosis (ALS), yet the lipid composition of the white matter, where the myelinated axons of motor neurons are located, remains uncharacterised. We aimed to comprehensively characterise how myelin is altered in ALS by assessing its...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/6/554 |
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| author | Gemma L. Sadler Katherine N. Lewis Vinod K. Narayana David P. De Souza Joel Mason Catriona McLean David G. Gonsalvez Bradley J. Turner Samantha K. Barton |
| author_facet | Gemma L. Sadler Katherine N. Lewis Vinod K. Narayana David P. De Souza Joel Mason Catriona McLean David G. Gonsalvez Bradley J. Turner Samantha K. Barton |
| author_sort | Gemma L. Sadler |
| collection | DOAJ |
| description | Lipid metabolism is profoundly dysregulated in amyotrophic lateral sclerosis (ALS), yet the lipid composition of the white matter, where the myelinated axons of motor neurons are located, remains uncharacterised. We aimed to comprehensively characterise how myelin is altered in ALS by assessing its lipid and protein composition. We isolated white matter from the motor cortex from post-mortem tissue of ALS patients (n = 8 sporadic ALS cases and n = 6 familial ALS cases) and age- and sex-matched controls (n = 8) and conducted targeted lipidomic analyses, qPCR for gene expression of relevant lipid metabolising enzymes and Western blotting for myelin proteins. We also quantified myelin density by using spectral confocal reflectance microscopy (SCoRe). Whilst myelin protein composition was similar in ALS and control tissue, both the lipid levels and the expression of their corresponding enzymes were dysregulated, highlighting altered lipid metabolism in the white matter as well as a likely change in myelin composition. Altered myelin composition could contribute to motor neuron dysfunction, and this highlights how oligodendrocytes may play a critical role in ALS pathogenesis. |
| first_indexed | 2024-03-09T23:03:50Z |
| format | Article |
| id | doaj.art-49c0bc6a1ccb4261847a971c9dbde020 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T23:03:50Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-49c0bc6a1ccb4261847a971c9dbde0202023-11-23T17:56:35ZengMDPI AGMetabolites2218-19892022-06-0112655410.3390/metabo12060554Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral SclerosisGemma L. Sadler0Katherine N. Lewis1Vinod K. Narayana2David P. De Souza3Joel Mason4Catriona McLean5David G. Gonsalvez6Bradley J. Turner7Samantha K. Barton8Florey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaFlorey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaMetabolomics Australia, Bio21 Institute, University of Melbourne, Melbourne 3052, AustraliaMetabolomics Australia, Bio21 Institute, University of Melbourne, Melbourne 3052, AustraliaFlorey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaVictorian Brain Bank, Florey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaDepartment of Anatomy and Developmental Biology, Monash University, Melbourne 3168, AustraliaFlorey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaFlorey Institute of Neuroscience and Mental Health, Melbourne 3052, AustraliaLipid metabolism is profoundly dysregulated in amyotrophic lateral sclerosis (ALS), yet the lipid composition of the white matter, where the myelinated axons of motor neurons are located, remains uncharacterised. We aimed to comprehensively characterise how myelin is altered in ALS by assessing its lipid and protein composition. We isolated white matter from the motor cortex from post-mortem tissue of ALS patients (n = 8 sporadic ALS cases and n = 6 familial ALS cases) and age- and sex-matched controls (n = 8) and conducted targeted lipidomic analyses, qPCR for gene expression of relevant lipid metabolising enzymes and Western blotting for myelin proteins. We also quantified myelin density by using spectral confocal reflectance microscopy (SCoRe). Whilst myelin protein composition was similar in ALS and control tissue, both the lipid levels and the expression of their corresponding enzymes were dysregulated, highlighting altered lipid metabolism in the white matter as well as a likely change in myelin composition. Altered myelin composition could contribute to motor neuron dysfunction, and this highlights how oligodendrocytes may play a critical role in ALS pathogenesis.https://www.mdpi.com/2218-1989/12/6/554ALSmyelinlipid metabolism |
| spellingShingle | Gemma L. Sadler Katherine N. Lewis Vinod K. Narayana David P. De Souza Joel Mason Catriona McLean David G. Gonsalvez Bradley J. Turner Samantha K. Barton Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis Metabolites ALS myelin lipid metabolism |
| title | Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis |
| title_full | Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis |
| title_fullStr | Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis |
| title_short | Lipid Metabolism Is Dysregulated in the Motor Cortex White Matter in Amyotrophic Lateral Sclerosis |
| title_sort | lipid metabolism is dysregulated in the motor cortex white matter in amyotrophic lateral sclerosis |
| topic | ALS myelin lipid metabolism |
| url | https://www.mdpi.com/2218-1989/12/6/554 |
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