Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still n...
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MDPI AG
2023-10-01
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| author | Sofia Pereira das Neves João Carlos Sousa Ricardo Magalhães Fuying Gao Giovanni Coppola Sebatien Mériaux Fawzi Boumezbeur Nuno Sousa João José Cerqueira Fernanda Marques |
| author_facet | Sofia Pereira das Neves João Carlos Sousa Ricardo Magalhães Fuying Gao Giovanni Coppola Sebatien Mériaux Fawzi Boumezbeur Nuno Sousa João José Cerqueira Fernanda Marques |
| author_sort | Sofia Pereira das Neves |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes’ transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize “astrocyte reactivity”. Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS. |
| first_indexed | 2024-03-10T21:21:55Z |
| format | Article |
| id | doaj.art-c6a7058d971d4d6da104d691d7ab89c3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:21:55Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c6a7058d971d4d6da104d691d7ab89c32023-11-19T16:02:49ZengMDPI AGCells2073-44092023-10-011220248410.3390/cells12202484Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal ModelSofia Pereira das Neves0João Carlos Sousa1Ricardo Magalhães2Fuying Gao3Giovanni Coppola4Sebatien Mériaux5Fawzi Boumezbeur6Nuno Sousa7João José Cerqueira8Fernanda Marques9Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalNeuroSpin, CEA, Paris-Saclay University, Centre d’études de Saclay, Bâtiment 145, 91191 Gif-sur-Yvette, FranceProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USAProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USANeuroSpin, CEA, Paris-Saclay University, Centre d’études de Saclay, Bâtiment 145, 91191 Gif-sur-Yvette, FranceNeuroSpin, CEA, Paris-Saclay University, Centre d’études de Saclay, Bâtiment 145, 91191 Gif-sur-Yvette, FranceLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes’ transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize “astrocyte reactivity”. Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS.https://www.mdpi.com/2073-4409/12/20/2484multiple sclerosisastrocytesmetabolismglycolysisTCA cycle |
| spellingShingle | Sofia Pereira das Neves João Carlos Sousa Ricardo Magalhães Fuying Gao Giovanni Coppola Sebatien Mériaux Fawzi Boumezbeur Nuno Sousa João José Cerqueira Fernanda Marques Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model Cells multiple sclerosis astrocytes metabolism glycolysis TCA cycle |
| title | Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model |
| title_full | Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model |
| title_fullStr | Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model |
| title_full_unstemmed | Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model |
| title_short | Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model |
| title_sort | astrocytes undergo metabolic reprogramming in the multiple sclerosis animal model |
| topic | multiple sclerosis astrocytes metabolism glycolysis TCA cycle |
| url | https://www.mdpi.com/2073-4409/12/20/2484 |
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