Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-29T05:59:28.182Z Has data issue: false hasContentIssue false

α-B-Crystallin as a Tissue Marker of Epileptic Foci in Paediatric Resections

Published online by Cambridge University Press:  02 December 2014

Harvey B. Sarnat*
Affiliation:
Departments of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences, Alberta Children’s Hospital and University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
Laura Flores-Sarnat
Affiliation:
Departments of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences, Alberta Children’s Hospital and University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
*
Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8, Canada Email: harvey.sarnat@albertahealthservices.ca
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

We studied α-B-crystallin, a small heat shock chaperone protein upregulated by various “stresses”, as an immunocytochemical tissue marker of epileptic foci.

Methods:

We examined 45 resected brain tissues of epileptic patients, 16 months to 23 years. Postmortem brains of 2 epileptic children and 20 normal fetuses and neonates of 10-41 weeks gestation similarly were studied. Immunocytochemical demonstration of α-B-crystallin was supplemented by neuronal, glial and inflammatory cell markers and electron microscopy (EM) in surgical cases. Autopsy brain tissue of children without epilepsy or neurological disease served as controls.

Results:

In all resections, α-B-crystallin was overexpressed in astrocytes and oligodendrocytes, including satellite cells adherent to neurons, and occasionally in neurons of neocortex, hippocampus and amygdala. In six cases, reactivity was most intense at or near the epileptic focus, with a diminishing gradient of intensity for 2-3 cm; similar focal expression was seen in autopsy cases. Presence or absence of histological structural lesions was independent of α-B-crystallin expression. Balloon cells and giant atypical cells in tuberous sclerosis were intensely reactive. Reactivity was present in DNETs. No correlation occurred with microglial activation, inflammation or gliosis; no ultrastructural alterations were seen. No expression was seen in fetal brains at any age.

Conclusions:

Immunoreactive α-B-crystallin is a reliable tissue marker of epileptic foci, regardless of presence or absence of structural lesions; at times it maps the extent of a focus.

Type
Original Article
Copyright
Copyright © The Canadian Journal of Neurological 2009

References

1.Schramm, J.Temporal lobe epilepsy surgery and the quest for optimal extent of resection: a review. Epilepsia. 2008;49: 1296307Google Scholar
2.Aull-Watschinger, S, Pataraia, E, Czech, T, Baumgartner, C.Outcome predictors for surgical treatment of temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2008;49:130816Google Scholar
3.Uijl, SG, Leijten, FSS, Arends, JBAM, Parra, J, van Huffelen, AC, Moons, KGM.Prognosis after temporal lobe epilepsy surgery: the value of combining predictors. Epilepsia. 2008;49:131723CrossRefGoogle ScholarPubMed
4.Kappe, G, Franck, E, Verschuure, P, Boelens, WC, Leunissen, JA, de Jong, WW.The human genome encodes 10 α-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones. 2003;8:5361Google Scholar
5.Koteiche, HA, McHaourab, HS.Mechanism of a hereditary cataract phenotype. Mutations in alpha-crystallin activate substrate binding. J Biol Chem. 2006;281:142739Google Scholar
6.Andley, UP.Crystallins in the eye: function and pathology. Progr Retin Eye Res. 2007;26:7898Google Scholar
7.Yang, T, Hsu, C, Liao, W, Chuang, JS.Heat shock protein 70 expression in epilepsy suggests stress rather than protection. Acta Neuropathol. 2008;115:21930Google Scholar
8.Ferns, G, Shams, S, Shafi, S.Heat shock protein 27: its potential role in vascular disease. Int J Exp Pathol. 2006;87:25374Google Scholar
9.Dorland’s Illustrated Medical Dictionary. 30th ed. Philadelphia: WB Saunders; 2003. p. 341.Google Scholar
10.Takeuchi, S, Mandai, Y, Otsu, A, Shirakawa, T, Masuda, K, Chinami, M.Differences in properties between human α-A- and α-B-Crystallin proteins expressed in Escherichia coli cells in response to cold and extreme pH. Biochem J. 2003;375(Pt 2):4715.CrossRefGoogle Scholar
11.Link, CD, Taft, A, Kapulkin, V, Duke, K, Kim, S, Fei, Q, et al.Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer’s disease model. Neurobiol Aging. 2003;24:397413Google Scholar
12.Adly, MA, Assaf, A, Hussein, MR.Expression of the head shock protein-27 in the adult human scalp skin and hair follicle: hair cycle-dependent changes. J Am Acad Dermatol. 2006;54:81117Google Scholar
13.Melloni’s Illustrated Medical Dictionary. 4th ed. London, UK: Parthenon Publishing Group; 2002. p. 120.Google Scholar
14.Median, S, Knowles, TP, Baldwin, AJ, Smith, JF, Squires, AM, Clements, P, et al.Characterisation of amyloid fibril formation by small heat-shock chaperone proteins human alpha-A-, alpha-B- and R120G alpha-B-crystallins. J Mol Biol. 2007;372:47084Google Scholar
15.Fujita, Y, Ohto, E, Katayama, E, Atomi, Y.α-B-crystallin-coated MAP microtubule resists nocodazole and calcium-induced disassembly. J Cell Sci. 2004;117:171926CrossRefGoogle ScholarPubMed
16.Aquilina, JA, Benesch, JL, Ding, LL, Yaron, O, Horwitz, J, Robinson, CV.Phosphorylation of α-B-crystallin alters chaperone function through loss of dimeric substructure. J Biol Chem, 2004;279: 2867580CrossRefGoogle ScholarPubMed
17.Ohto-Fujita, E, Fujita, Y, Atomi, Y.Analysis of the alphaB-crystallin domain responsible for inhibiting tubulin aggregation. Cell Stress Chaperones. 2007;12:16371Google Scholar
18.Sakurai, T, Fujita, T, Ohto, E, Oguro, A, Atomi, Y.The decrease of the cytoskeleton tubulin follows the decrease of the associating molecular chaperone α-B-crystallin in unloaded soleus muscle atrophy without stretch. FASEB J. 2005;19:1199201Google Scholar
19.den Engelsman, J, Gerrits, D, de Jong, WW, Robbins, J, Kato, K, Boelens, WC.Nuclear import of {alpha}B-crystallin is phosphorylation-dependent and hampered by hyper-phosphorylation of the myopathy-related mutant R120G. J Biol Chem. 2005;280:3713948Google Scholar
20.Launay, N, Goudeau, B, Kato, K, Vicart, P, Lilienbaum, A.Cell signaling to α-B-crystallin following stresses of the cytoskeleton. Exp Cell Res. 2006;312:357084Google Scholar
21.Ecroyd, H, Meehan, S, Horwitz, J, Aquilina, JA, Benesch, JL, Robinson, CV, et al.Mimicking phosphorylation of α-B-crystallin affects its chaperone activity. Biochem J. 2007;401:12941Google Scholar
22.Fujii, N, Nakamura, T, Sadakane, Y, Saito, T, Fujii, N.Differential susceptibility of alpha-A- and alpha-B-crystallin to gamma-ray irradiation. Biochim Biophys Acta. 2007;1774:34550Google Scholar
23.Hirose, T, Scheithauer, BW, Lopes, MB, VanderBerg, SR.Dysembryoplastic neuroepithelial tumor (DNT): an immunohistochemical and ultrastructural study. J Neuropathol Exp Neurol. 1994;53:18495CrossRefGoogle ScholarPubMed
24.Prayson, RA, Morris, HH, Estes, MI, Comair, YG.Dysembryoplastic neuroepithelial tumor: a clinicopathological and immuno-histochemical study of 11 tumors including MIB1 immuno-reactivity. Clin Neuropathol. 1996;15:4753Google Scholar
25.Honavar, M, Janota, I, Polkey, CE.Histological heterogeneity of dysembryoplastic neuroepithelial tumors: identification and differential diagnosis in a series of 74 cases. Histopathology. 1999;34:34256CrossRefGoogle Scholar
26.Lee, M-C, Kang, JY, Seol, MB, Kim, HS, Woo, JY, Lee, JS, et al.Clinical features and epileptogenesis of dysembryoplastic neuroepithelial tumor. Child’s Nerv Syst. 2006;22:161118Google Scholar
27.Ha, Y, Kim, TS, Yoon, DH, Cho, YE, Huh, SG, Lee, KC.Reinduced expression of developmental proteins (nestin, small heat shock protein) in and around cerebral arteriovenous malformations. Clin Neuropathol. 2003;22:25261Google Scholar
28.Skalnikova, H, Halada, P, Vodicka, P, Motlik, J, Rehulka, P, Horning, O, et al.A proteomic approach to studying the differentiation of neural stem cells. Proteomics. 2007;7:182538Google Scholar
29.Quinlan, RA, Brenner, M, Goldman, JE, Messing, A.GFAP and its role in Alexander disease. Exp Cell Res. 2007;313:207787Google Scholar
30.Biber, K, Neumann, H, Inoue, K, Boddeke, HWGM.Neuronal ‘on’ and ‘off’ signals control microglia. Trends Neurosci. 2007;30:596602Google Scholar