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

• Published in: Clinical and experimental immunology Vol. 194; no. 2; pp. 137 - 152
• Main Authors: Gorter, R. P., Nutma, E., Jahrei, M.‐C., de Jonge, J. C., Quinlan, R. A, Valk, P., Noort, J. M., Baron, W., Amor, S.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2018; John Wiley and Sons Inc
• Subjects: Adult; Aged; Aged, 80 and over; alpha‐B crystallin; Astrocytes; Astrocytes - metabolism; Brain; Brain - pathology; Central nervous system; Chemical compounds; Cytoskeleton; Demyelinating Diseases; Demyelination; Female; Gray Matter - metabolism; Gray Matter - pathology; Heat shock proteins; Heat-Shock Proteins - metabolism; HSP16.2; HSPB1; HSPB11; HSPB5; HSPB6; HSPB8; HSPBs; Humans; Immunohistochemistry; Lesions; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - metabolism; Neurodegeneration; Neurons - metabolism; Original; pathology; Pharmaceuticals; Proteins; Small heat shock proteins; Spinal cord; Spinal Cord - pathology; Tissues; Western blotting; White Matter - metabolism; White Matter - pathology; pathology; HSPB6; HSPB5; HSPB8; multiple sclerosis; alpha-B crystallin; HSPB1; HSPBs; spinal cord; HSPB11; HSP16.2
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13186

Summary Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized 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. In this study we have compared brain and spinal cord white (WM) and grey (GM) matter from MS and control tissues, focusing on small heat shock proteins (HSPB) and HSP16.2. 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. 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 GM and type 1 GM lesions. 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. Multiple sclerosis is a chronic inflammatory disease affecting the whole of the CNS yet very few studies detail the pathology of the spinal cord. Here we show regional differences in HSP expression with higher constitutive expression of HSP in the spinal cord. This may reflect differences in astrocyte cytoskeleton composition, influence the degree of inflammation and thus damage. Such pathological differences are key to understanding diseases processes that may affect local effectiveness of pharmacological agents.