TY - JOUR
T1 - Increased expression of complement components in tuberous sclerosis complex and focal cortical dysplasia type 2B brain lesions
AU - Gruber, Victoria-Elisabeth
AU - Luinenburg, Mark J.
AU - Colleselli, Katrin
AU - Endmayr, Verena
AU - Anink, Jasper J.
AU - Zimmer, Till S.
AU - Jansen, Floor
AU - Gosselaar, Peter
AU - Coras, Roland
AU - Scholl, Theresa
AU - Blumcke, Ingmar
AU - Pimentel, José
AU - Hainfellner, Johannes A.
AU - Höftberger, Romana
AU - Rössler, Karl
AU - Feucht, Martha
AU - van Scheppingen, Jackelien
AU - Aronica, Eleonora
AU - Mühlebner, Angelika
N1 - Funding Information: V.‐E.G. was funded by a grant of the Austrian Epilepsy Society dedicated to M.F. and by the German Tuberous Sclerosis Association (T.S., V.‐E.G.). The research leading to these results has also received funding from the European Union's Seventh Framework Program (FP7/2007‐2013) under grant agreement 602391 (EPISTOP; E.A., M.F., A.M., T.S.); the Dutch Epilepsy Foundation (project number 2020‐02; A.M., M.J.L., J.v.S.); the ZonMw Translational Research Program (95105004); and the European Union's Horizon 2020 WIDESPREAD‐05‐2020–Twinning, EpiEpiNet (grant agreement 952455; E.A.). Publisher Copyright: © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2021
Y1 - 2021
N2 - Objective: Increasing evidence supports the contribution of inflammatory mechanisms to the neurological manifestations of epileptogenic developmental pathologies linked to mammalian target of rapamycin (mTOR) pathway dysregulation (mTORopathies), such as tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD). In this study, we aimed to investigate the expression pattern and cellular distribution of the complement factors C1q and C3 in resected cortical tissue of clinically well-characterized patients with TSC and FCD2B. Methods: We applied immunohistochemistry in TSC (n = 29) and FCD2B (n = 32) samples and compared them to autopsy and biopsy controls (n = 27). Furthermore, protein expression was observed via Western blot, and for descriptive colocalization studies immunofluorescence double labeling was performed. Results: Protein expression for C3 was significantly upregulated in TSC and FCD2B white and gray matter lesions compared to controls. Staining of the synaptic vesicle protein synaptophysin showed a remarkable increase in the white matter of both TSC and FCD2B. Furthermore, confocal imaging revealed colocalization of complement factors with astroglial, microglial, neuronal, and abnormal cells in various patterns. Significance: Our results demonstrate that the prominent activation of the complement pathway represents a common pathological hallmark of TSC and FCD2B, suggesting that complement overactivation may play a role in these mTORopathies.
AB - Objective: Increasing evidence supports the contribution of inflammatory mechanisms to the neurological manifestations of epileptogenic developmental pathologies linked to mammalian target of rapamycin (mTOR) pathway dysregulation (mTORopathies), such as tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD). In this study, we aimed to investigate the expression pattern and cellular distribution of the complement factors C1q and C3 in resected cortical tissue of clinically well-characterized patients with TSC and FCD2B. Methods: We applied immunohistochemistry in TSC (n = 29) and FCD2B (n = 32) samples and compared them to autopsy and biopsy controls (n = 27). Furthermore, protein expression was observed via Western blot, and for descriptive colocalization studies immunofluorescence double labeling was performed. Results: Protein expression for C3 was significantly upregulated in TSC and FCD2B white and gray matter lesions compared to controls. Staining of the synaptic vesicle protein synaptophysin showed a remarkable increase in the white matter of both TSC and FCD2B. Furthermore, confocal imaging revealed colocalization of complement factors with astroglial, microglial, neuronal, and abnormal cells in various patterns. Significance: Our results demonstrate that the prominent activation of the complement pathway represents a common pathological hallmark of TSC and FCD2B, suggesting that complement overactivation may play a role in these mTORopathies.
KW - complement
KW - cortical development
KW - epilepsy
KW - focal cortical dysplasia
KW - inflammation
KW - tuberous sclerosis complex
UR - http://www.scopus.com/inward/record.url?scp=85121326885&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/epi.17139
DO - https://doi.org/10.1111/epi.17139
M3 - Article
C2 - 34904712
SN - 0013-9580
JO - Epilepsia
JF - Epilepsia
ER -