Gorter, R. (Rianne) (2017) No Star is the Same : Differential HSPB5 Phosphorylation in Cortical and Spinal Cord Multiple Sclerosis Lesions Reveals Regional Heterogeneity of Astrogliosis. thesis, Medicine.
Full text available on request.Abstract
Introduction: In Multiple sclerosis (MS), demyelinating lesions affect the white matter (WM) and grey matter (GM) of brain, optic nerve and spinal cord, leading to cognitive, sensitive and motoric complications. Astrocytes, important cells in central nervous system (CNS) homeostasis, react to demyelination with ‘astrogliosis’. Astrogliosis is a spectrum of defensive changes in astrocytes that are generally beneficial to tissue repair, but on the long-term cause scar formation and reduce remyelination, ultimately leading to progressive degeneration in MS patients. Insight into heterogeneity of astrocytes across the CNS has increased our understanding of MS lesions in specific regions. Recently, phosphorylation of small heat shock protein 5 (HSPB5) at serine 59 was shown to facilitate astrogliosis in WM lesions, but its role in cortical and spinal cord lesions remained unclear. Methods: An in-depth pathological investigation was performed characterizing HSPB5 expression and phosphorylation in cortical and spinal cord lesions. Results: HSPB5 phosphorylation is strikingly absent in astrocytes in GM lesions, even in areas with relatively high levels of inflammation. In contrast to the brain, HSPB5 is increased in inactive lesions in the spinal cord. Moreover, HSPB5 serine 19 and HSPB5 serine 59 are present in morphologically distinct astrocytes in spinal cord lesions. Discussion: Regional differences in HSPB5 expression and phosphorylation, in WM/GM and brain/spinal cord, illustrate regional heterogeneity in astrogliosis, likely impacting remyelinating capacity. Unravelling the pathological differences will help to find more targeted treatments for cortical and spinal cord lesions, which cause cognitive and motor problems that heavily affect the quality of life of MS patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Baron, Dr. Wia |
| Supervisor name: | On-site supervisor: and Amor, Prof. Dr. Sandra and Department of Pathology and VUmc Medical Centre Amsterdam |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:42 |
| Last Modified: | 25 Jun 2020 10:42 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/410 |
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