Heat shock proteins are differentially expressed in brain and spinal cord: implications for multiple sclerosis

Gorter, Rianne P.; Nutma, Erik; Jahreiβ, Marie-Christina; de Jonge, Jenny C.; Quinlan, Roy; van der Valk, Paul; van Noort, Johannes M.; Baron, Wia; Amor, Sandra

Abstract

Aims: Multiple sclerosis (MS) is a chronic neurodegenerative disease characterised by demyelination, inflammation and neurodegeneration throughout the central nervous system. Although spinal cord pathology is an important factor contributing to disease progression, few studies have examined MS lesions in the spinal cord and how they differ from brain lesions. Here we have compared brain and spinal cord white and grey matter from MS and control tissues focussing on small heat shock proteins (HSPB) and HSP16.2. Methods: Western blotting was used to examine protein levels of HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 in brain and spinal cord from MS and age‐matched non‐neurological controls. Immunohistochemistry was used to examine expression of the HSPs in MS spinal cord lesions and controls. Expression levels were quantified using ImageJ. Results: Western blotting revealed significantly higher levels of HSPB1, HSPB6 and HSPB8 in MS and control spinal cord compared to brain tissues. No differences in HSPB5 and HSP16.2 protein levels were observed although HSPB5 protein levels were higher in brain WM versus GM. In MS spinal cord lesions, increased HSPB1 and HSPB5 expression was observed in astrocytes, and increased neuronal expression of HSP16.2 was observed in normal appearing grey matter and type 1 grey matter lesions. Conclusions: The high constitutive expression of several HSPBs in spinal cord and increased expression of HSPBs and HSP16.2 in MS illustrate differences between brain and spinal cord in health and upon demyelination. Regional differences in HSP expression may reflect differences in astrocyte cytoskeleton composition and influence inflammation, possibly affecting the effectiveness of pharmacological agents.

Citation

Gorter, R. P., Nutma, E., Jahreiβ, M.-C., de Jonge, J. C., Quinlan, R., van der Valk, P., van Noort, J. M., Baron, W., & Amor, S. (2018). Heat shock proteins are differentially expressed in brain and spinal cord: implications for multiple sclerosis. Clinical and Experimental Immunology, 194(2), 137-152. https://doi.org/10.1111/cei.13186

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2018
• Online Publication Date: Sep 19, 2018
• Publication Date: Nov 1, 2018
• Deposit Date: Jul 23, 2018
• Publicly Available Date: Oct 22, 2018
• Journal: Clinical and Experimental Immunology
• Print ISSN: 0009-9104
• Electronic ISSN: 1365-2249
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 194
• Issue: 2
• Pages: 137-152
• DOI: https://doi.org/10.1111/cei.13186
• Public URL: https://durham-repository.worktribe.com/output/1325450