An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis
Elevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone mod...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-12-01
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| Series: | ASN Neuro |
| Online Access: | https://doi.org/10.1177/17590914231198980 |
| _version_ | 1797398185541369856 |
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| author | Intakhar Ahmad Stig Wergeland Eystein Oveland Lars Bø |
| author_facet | Intakhar Ahmad Stig Wergeland Eystein Oveland Lars Bø |
| author_sort | Intakhar Ahmad |
| collection | DOAJ |
| description | Elevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone model in mice (CPZ), a model of toxic/metabolic demyelination and remyelination in different brain areas. In MS gray matter (GM), CHI3L1 was detected primarily in astrocytes and in a subset of pyramidal neurons. In neurons, CHI3L1 immunopositivity was associated with lipofuscin-like substance accumulation, a sign of cellular aging that can lead to cell death. The density of CHI3L1-positive neurons was found to be significantly higher in normal-appearing MS GM tissue compared to that of control subjects ( p = .014). In MS white matter (WM), CHI3L1 was detected in astrocytes located within lesion areas, as well as in perivascular normal-appearing areas and in phagocytic cells from the initial phases of lesion development. In the CPZ model, the density of CHI3L1-positive cells was strongly associated with microglial activation in the WM and choroid plexus inflammation. Compared to controls, CHI3L1 immunopositivity in WM was increased from an early phase of CPZ exposure. In the GM, CHI3L1 immunopositivity increased later in the CPZ exposure phase, particularly in the deep GM region. These results indicate that CHI3L1 is associated with neuronal deterioration, pre-lesion pathology, along with inflammation in MS. |
| first_indexed | 2024-03-09T01:22:07Z |
| format | Article |
| id | doaj.art-0866159352e74cfcb00d2bdae54caed7 |
| institution | Directory Open Access Journal |
| issn | 1759-0914 |
| language | English |
| last_indexed | 2024-03-09T01:22:07Z |
| publishDate | 2023-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | ASN Neuro |
| spelling | doaj.art-0866159352e74cfcb00d2bdae54caed72023-12-10T11:33:18ZengSAGE PublishingASN Neuro1759-09142023-12-011510.1177/17590914231198980An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple SclerosisIntakhar Ahmad0Stig Wergeland1Eystein Oveland2Lars Bø3 Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, , Bergen, Norway Neuro-SysMed, Haukeland University Hospital, Bergen, Norway , IMR, Bergen, Norway Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, , Bergen, NorwayElevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone model in mice (CPZ), a model of toxic/metabolic demyelination and remyelination in different brain areas. In MS gray matter (GM), CHI3L1 was detected primarily in astrocytes and in a subset of pyramidal neurons. In neurons, CHI3L1 immunopositivity was associated with lipofuscin-like substance accumulation, a sign of cellular aging that can lead to cell death. The density of CHI3L1-positive neurons was found to be significantly higher in normal-appearing MS GM tissue compared to that of control subjects ( p = .014). In MS white matter (WM), CHI3L1 was detected in astrocytes located within lesion areas, as well as in perivascular normal-appearing areas and in phagocytic cells from the initial phases of lesion development. In the CPZ model, the density of CHI3L1-positive cells was strongly associated with microglial activation in the WM and choroid plexus inflammation. Compared to controls, CHI3L1 immunopositivity in WM was increased from an early phase of CPZ exposure. In the GM, CHI3L1 immunopositivity increased later in the CPZ exposure phase, particularly in the deep GM region. These results indicate that CHI3L1 is associated with neuronal deterioration, pre-lesion pathology, along with inflammation in MS.https://doi.org/10.1177/17590914231198980 |
| spellingShingle | Intakhar Ahmad Stig Wergeland Eystein Oveland Lars Bø An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis ASN Neuro |
| title | An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis |
| title_full | An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis |
| title_fullStr | An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis |
| title_full_unstemmed | An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis |
| title_short | An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis |
| title_sort | association of chitinase 3 like protein 1 with neuronal deterioration in multiple sclerosis |
| url | https://doi.org/10.1177/17590914231198980 |
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