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3. Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex

Author

Scheper, Mirte, Sørensen, Frederik N. F., Ruffolo, Gabriele, Gaeta, Alessandro, Lissner, Lilian J., Anink, Jasper J., Korshunova, Irina, Jansen, Floor E., Riney, Kate, van Hecke, Wim, Mühlebner, Angelika, Khodosevich, Konstantin, Schubert, Dirk, Palma, Eleonora, Mills, James D., and Aronica, Eleonora

Published
2024
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4. Astroglial calcium signaling and homeostasis in tuberous sclerosis complex

Author

Romagnolo, Alessia, Dematteis, Giulia, Scheper, Mirte, Luinenburg, Mark J., Mühlebner, Angelika, Van Hecke, Wim, Manfredi, Marcello, De Giorgis, Veronica, Reano, Simone, Filigheddu, Nicoletta, Bortolotto, Valeria, Tapella, Laura, Anink, Jasper J., François, Liesbeth, Dedeurwaerdere, Stefanie, Mills, James D., Genazzani, Armando A., Lim, Dmitry, and Aronica, Eleonora

Published
2024
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6. Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents

Author

Cho, Frances S, Vainchtein, Ilia D, Voskobiynyk, Yuliya, Morningstar, Allison R, Aparicio, Francisco, Higashikubo, Bryan, Ciesielska, Agnieszka, Broekaart, Diede WM, Anink, Jasper J, van Vliet, Erwin A, Yu, Xinzhu, Khakh, Baljit S, Aronica, Eleonora, Molofsky, Anna V, and Paz, Jeanne T

Subjects
Biomedical and Clinical Sciences, Neurosciences, Physical Injury - Accidents and Adverse Effects, Prevention, Epilepsy, Brain Disorders, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Animals, Astrocytes, Brain Injuries, COVID-19, Disease Models, Animal, GABA Plasma Membrane Transport Proteins, Inflammation, Mice, Polymers, Rodentia, SARS-CoV-2, Seizures, Thalamus, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

Published
2022

7. Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

Author

Huschner, Franz, Głowacka-Walas, Jagoda, Mills, James D., Klonowska, Katarzyna, Lasseter, Kathryn, Asara, John M., Moavero, Romina, Hertzberg, Christoph, Weschke, Bernhard, Riney, Kate, Feucht, Martha, Scholl, Theresa, Krsek, Pavel, Nabbout, Rima, Jansen, Anna C., Petrák, Bořivoj, van Scheppingen, Jackelien, Zamecnik, Josef, Iyer, Anand, Anink, Jasper J., Mühlebner, Angelika, Mijnsbergen, Caroline, Lagae, Lieven, Curatolo, Paolo, Borkowska, Julita, Sadowski, Krzysztof, Domańska-Pakieła, Dorota, Blazejczyk, Magdalena, Jansen, Floor E., Janson, Stef, Urbanska, Malgorzata, Tempes, Aleksandra, Janssen, Bart, Sijko, Kamil, Wojdan, Konrad, Jozwiak, Sergiusz, Kotulska, Katarzyna, Lehmann, Karola, Aronica, Eleonora, Jaworski, Jacek, and Kwiatkowski, David J.

Published
2023
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8. Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

Author

Bongaarts, Anika, Mijnsbergen, Caroline, Anink, Jasper J., Jansen, Floor E., Spliet, Wim G. M., den Dunnen, Wilfred F. A., Coras, Roland, Blümcke, Ingmar, Paulus, Werner, Gruber, Victoria E., Scholl, Theresa, Hainfellner, Johannes A., Feucht, Martha, Kotulska, Katarzyna, Jozwiak, Sergiusz, Grajkowska, Wieslawa, Buccoliero, Anna Maria, Caporalini, Chiara, Giordano, Flavio, Genitori, Lorenzo, Söylemezoğlu, Figen, Pimentel, José, Jones, David T. W., Scicluna, Brendon P., Schouten-van Meeteren, Antoinette Y. N., Mühlebner, Angelika, Mills, James D., and Aronica, Eleonora

Published
2022
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9. Author Correction: Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment

Author

Mills, James D., Iyer, Anand M., van Scheppingen, Jackelien, Bongaarts, Anika, Anink, Jasper J., Janssen, Bart, Zimmer, Till S., Spliet, Wim G., van Rijen, Peter C., Jansen, Floor E., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Kotulska, Katarzyna, Jozwiak, Sergiusz, Jansen, Anna, Lagae, Lieven, Curatolo, Paolo, Kwiatkowski, David J., Pasterkamp, R. Jeroen, Senthilkumar, Ketharini, von Oerthel, Lars, Hoekman, Marco F., Gorter, Jan A., Crino, Peter B., Mühlebner, Angelika, Scicluna, Brendon P., and Aronica, Eleonora

Published
2022
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10. Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period

Author

Korotkov, Anatoly, Luinenburg, Mark J., Romagnolo, Alessia, Zimmer, Till S., van Scheppingen, Jackelien, Bongaarts, Anika, Broekaart, Diede W. M., Anink, Jasper J., Mijnsbergen, Caroline, Jansen, Floor E., van Hecke, Wim, Spliet, Wim G., van Rijen, Peter C., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Crino, Peter B., Kotulska, Katarzyna, Lagae, Lieven, Jansen, Anna C., Kwiatkowski, David J., Jozwiak, Sergiusz, Curatolo, Paolo, Mühlebner, Angelika, van Vliet, Erwin A., Mills, James D., and Aronica, Eleonora

Published
2022
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11. Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex

Author

Neurologen, Brain, Pathologie Pathologen staf, Cancer, Scheper, Mirte, Sørensen, Frederik N F, Ruffolo, Gabriele, Gaeta, Alessandro, Lissner, Lilian J, Anink, Jasper J, Korshunova, Irina, Jansen, Floor E, Riney, Kate, van Hecke, Wim, Mühlebner, Angelika, Khodosevich, Konstantin, Schubert, Dirk, Palma, Eleonora, Mills, James D, Aronica, Eleonora, Neurologen, Brain, Pathologie Pathologen staf, Cancer, Scheper, Mirte, Sørensen, Frederik N F, Ruffolo, Gabriele, Gaeta, Alessandro, Lissner, Lilian J, Anink, Jasper J, Korshunova, Irina, Jansen, Floor E, Riney, Kate, van Hecke, Wim, Mühlebner, Angelika, Khodosevich, Konstantin, Schubert, Dirk, Palma, Eleonora, Mills, James D, and Aronica, Eleonora

Published
2024

12. Identification of gene regulatory networks affected across drug-resistant epilepsies

Author

Pathologie Pathologen staf, Brain, Cancer, Pathologie, François, Liesbeth, Romagnolo, Alessia, Luinenburg, Mark J, Anink, Jasper J, Godard, Patrice, Rajman, Marek, van Eyll, Jonathan, Mühlebner, Angelika, Skelton, Andrew, Mills, James D, Dedeurwaerdere, Stefanie, Aronica, Eleonora, Pathologie Pathologen staf, Brain, Cancer, Pathologie, François, Liesbeth, Romagnolo, Alessia, Luinenburg, Mark J, Anink, Jasper J, Godard, Patrice, Rajman, Marek, van Eyll, Jonathan, Mühlebner, Angelika, Skelton, Andrew, Mills, James D, Dedeurwaerdere, Stefanie, and Aronica, Eleonora

Published
2024

13. Astroglial calcium signaling and homeostasis in tuberous sclerosis complex

Author

Pathologie Pathologen staf, Brain, Cancer, Pathologie, Romagnolo, Alessia, Dematteis, Giulia, Scheper, Mirte, Luinenburg, Mark J, Mühlebner, Angelika, Van Hecke, Wim, Manfredi, Marcello, De Giorgis, Veronica, Reano, Simone, Filigheddu, Nicoletta, Bortolotto, Valeria, Tapella, Laura, Anink, Jasper J, François, Liesbeth, Dedeurwaerdere, Stefanie, Mills, James D, Genazzani, Armando A, Lim, Dmitry, Aronica, Eleonora, Pathologie Pathologen staf, Brain, Cancer, Pathologie, Romagnolo, Alessia, Dematteis, Giulia, Scheper, Mirte, Luinenburg, Mark J, Mühlebner, Angelika, Van Hecke, Wim, Manfredi, Marcello, De Giorgis, Veronica, Reano, Simone, Filigheddu, Nicoletta, Bortolotto, Valeria, Tapella, Laura, Anink, Jasper J, François, Liesbeth, Dedeurwaerdere, Stefanie, Mills, James D, Genazzani, Armando A, Lim, Dmitry, and Aronica, Eleonora

Published
2024

14. Loss of maturity and homeostatic functions in Tuberous Sclerosis Complex-derived astrocytes

Author

Luinenburg, Mark J., primary, Scheper, Mirte, additional, Sørensen, Frederik N. F., additional, Anink, Jasper J., additional, Van Hecke, Wim, additional, Korshunova, Irina, additional, Jansen, Floor E., additional, Riney, Kate, additional, van Eijsden, Pieter, additional, Gosselaar, Peter, additional, Mills, James D., additional, Kalf, Rozemarijn S., additional, Zimmer, Till S., additional, Broekaart, Diede W. M., additional, Khodosevich, Konstantin, additional, Aronica, Eleonora, additional, and Mühlebner, Angelika, additional

Published
2023
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15. Dysregulation of miR-543 in Parkinson's disease:Impact on the neuroprotective gene SIRT1

Author

Scheper, Mirte, Iyer, Anand, Anink, Jasper J., Mesarosova, Lucia, Mills, James D., Aronica, Eleonora, Scheper, Mirte, Iyer, Anand, Anink, Jasper J., Mesarosova, Lucia, Mills, James D., and Aronica, Eleonora

Abstract

Aims: Parkinson's disease (PD) is a progressive and age-dependent neurodegenerative disease characterised clinically by a variety of motor symptoms and cognitive impairment. PD was initially considered to be a grey matter disease; however, recently, evidence has emerged that white matter changes in PD precede the neuronal loss seen in the grey matter. The cause of these initial white matter changes is yet to be elucidated. Here, we explored whether dysregulated miRNAs and their target mRNA could provide insight into the underlying mechanisms of early white matter changes in PD. Methods: We analysed the expression of miRNAs in three different stages of PD through RNA-sequencing and validated the differential expression of miRNAs through quantitative reverse transcription polymerase chain reaction. With bioinformatic analyses, we predicted target genes of dysregulated miRNAs and investigated their biomarker potential. Finally, in vitro, we confirmed the targetting of the gene SIRT1 by miR-543. Results: We identified 12 dysregulated miRNAs in PD and found that miR-543 holds potential as a biomarker for late-stage PD with dementia. We report upregulation of miR-543 in early PD white matter tissue and downregulation of SIRT1. In vitro experiments showed that the upregulation of miR-543 results in the downregulation of SIRT1 in the white matter, but not in the grey matter. Conclusions: We validated SIRT1 as a target of miR-543 in the brain and showed its function as a potential biomarker. Our results highlight the idea that dysregulation of miR-543 in early PD white matter, resulting in the dysregulation of SIRT1, potentially influencing the early white matter changes observed in PD.

Published
2023

16. Loss of maturity and homeostatic functions in Tuberous Sclerosis Complex-derived astrocytes

Author

Pathologie Pathologen staf, Cancer, Neurologen, Brain, Neurochirurgen, Pathologie, Luinenburg, Mark J, Scheper, Mirte, Sørensen, Frederik N F, Anink, Jasper J, Van Hecke, Wim, Korshunova, Irina, Jansen, Floor E, Riney, Kate, van Eijsden, Pieter, Gosselaar, Peter, Mills, James D, Kalf, Rozemarijn S, Zimmer, Till S, Broekaart, Diede W M, Khodosevich, Konstantin, Aronica, Eleonora, Mühlebner, Angelika, Pathologie Pathologen staf, Cancer, Neurologen, Brain, Neurochirurgen, Pathologie, Luinenburg, Mark J, Scheper, Mirte, Sørensen, Frederik N F, Anink, Jasper J, Van Hecke, Wim, Korshunova, Irina, Jansen, Floor E, Riney, Kate, van Eijsden, Pieter, Gosselaar, Peter, Mills, James D, Kalf, Rozemarijn S, Zimmer, Till S, Broekaart, Diede W M, Khodosevich, Konstantin, Aronica, Eleonora, and Mühlebner, Angelika

Published
2023

17. Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years

Author

Pathologie Pathologen staf, Brain, Cancer, Pathologie Groep Van Diest, Neurologen, Pathologie, Huschner, Franz, Głowacka-Walas, Jagoda, Mills, James D, Klonowska, Katarzyna, Lasseter, Kathryn, Asara, John M, Moavero, Romina, Hertzberg, Christoph, Weschke, Bernhard, Riney, Kate, Feucht, Martha, Scholl, Theresa, Krsek, Pavel, Nabbout, Rima, Jansen, Anna C, Petrák, Bořivoj, van Scheppingen, Jackelien, Zamecnik, Josef, Iyer, Anand, Anink, Jasper J, Mühlebner, Angelika, Mijnsbergen, Caroline, Lagae, Lieven, Curatolo, Paolo, Borkowska, Julita, Sadowski, Krzysztof, Domańska-Pakieła, Dorota, Blazejczyk, Magdalena, Jansen, Floor E, Janson, Stef, Urbanska, Malgorzata, Tempes, Aleksandra, Janssen, Bart, Sijko, Kamil, Wojdan, Konrad, Jozwiak, Sergiusz, Kotulska, Katarzyna, Lehmann, Karola, Aronica, Eleonora, Jaworski, Jacek, Kwiatkowski, David J, Pathologie Pathologen staf, Brain, Cancer, Pathologie Groep Van Diest, Neurologen, Pathologie, Huschner, Franz, Głowacka-Walas, Jagoda, Mills, James D, Klonowska, Katarzyna, Lasseter, Kathryn, Asara, John M, Moavero, Romina, Hertzberg, Christoph, Weschke, Bernhard, Riney, Kate, Feucht, Martha, Scholl, Theresa, Krsek, Pavel, Nabbout, Rima, Jansen, Anna C, Petrák, Bořivoj, van Scheppingen, Jackelien, Zamecnik, Josef, Iyer, Anand, Anink, Jasper J, Mühlebner, Angelika, Mijnsbergen, Caroline, Lagae, Lieven, Curatolo, Paolo, Borkowska, Julita, Sadowski, Krzysztof, Domańska-Pakieła, Dorota, Blazejczyk, Magdalena, Jansen, Floor E, Janson, Stef, Urbanska, Malgorzata, Tempes, Aleksandra, Janssen, Bart, Sijko, Kamil, Wojdan, Konrad, Jozwiak, Sergiusz, Kotulska, Katarzyna, Lehmann, Karola, Aronica, Eleonora, Jaworski, Jacek, and Kwiatkowski, David J

Published
2023

18. Loss of maturity and homeostatic functions in Tuberous Sclerosis Complex-derived astrocytes

Author

Luinenburg, Mark J., Scheper, Mirte, Sørensen, Frederik N.F., Anink, Jasper J., Van Hecke, Wim, Korshunova, Irina, Jansen, Floor E., Riney, Kate, van Eijsden, Pieter, Gosselaar, Peter, Mills, James D., Kalf, Rozemarijn S., Zimmer, Till S., Broekaart, Diede W.M., Khodosevich, Konstantin, Aronica, Eleonora, Mühlebner, Angelika, Luinenburg, Mark J., Scheper, Mirte, Sørensen, Frederik N.F., Anink, Jasper J., Van Hecke, Wim, Korshunova, Irina, Jansen, Floor E., Riney, Kate, van Eijsden, Pieter, Gosselaar, Peter, Mills, James D., Kalf, Rozemarijn S., Zimmer, Till S., Broekaart, Diede W.M., Khodosevich, Konstantin, Aronica, Eleonora, and Mühlebner, Angelika

Abstract

Introduction: Constitutive activation of the mTOR pathway, as observed in Tuberous Sclerosis Complex (TSC), leads to glial dysfunction and subsequent epileptogenesis. Although astrocytes are considered important mediators for synaptic clearance and phagocytosis, little is known on how astrocytes contribute to the epileptogenic network. Methods: We employed singlenuclei RNA sequencing and a hybrid fetal calf serum (FCS)/FCS-free cell culture model to explore the capacity of TSC-derived astrocytes to maintain glutamate homeostasis and clear debris in their environment. Results: We found that TSC astrocytes show reduced maturity on RNA and protein level as well as the inability to clear excess glutamate through the loss of both enzymes and transporters complementary to a reduction of phagocytic capabilities. Discussion: Our study provides evidence of mechanistic alterations in TSC astrocytes, underscoring the significant impairment of their supportive functions. These insights enhance our understanding of TSC pathophysiology and hold potential implications for future therapeutic interventions.

Published
2023

19. The matrix metalloproteinase inhibitor IPR-179 has antiseizure and antiepileptogenic effects

Author

Broekaart, Diede W.M., Bertran, Alexandra, Jia, Shaobo, Korotkov, Anatoly, Senkov, Oleg, Bongaarts, Anika, Mills, James D., Anink, Jasper J., Seco, Jesus, Baayen, Johannes C., Idema, Sander, Chabrol, Elodie, Becker, Albert J., Wadman, Wytse J., Tarrago, Teresa, Gorter, Jan A., Aronica, Eleonora, Prades, Roger, Dityatev, Alexander, and van Vliet, Erwin A.

Subjects
Seizures (Medicine) -- Development and progression -- Drug therapy, Enzyme inhibitors -- Patient outcomes, Neuroplasticity -- Health aspects, Health care industry
Abstract

Matrix metalloproteinases (MMPs) are synthesized by neurons and glia and released into the extracellular space, where they act as modulators of neuroplasticity and neuroinflammatory agents. Development of epilepsy (epileptogenesis) is associated with increased expression of MMPs, and therefore, they may represent potential therapeutic drug targets. Using quantitative PCR (qPCR) and immunohistochemistry, we studied the expression of MMPs and their endogenous inhibitors tissue inhibitors of metalloproteinases (TIMPs) in patients with status epilepticus (SE) or temporal lobe epilepsy (TLE) and in a rat TLE model. Furthermore, we tested the MMP2/9 inhibitor IPR-179 in the rapid-kindling rat model and in the intrahippocampal kainic acid mouse model. In both human and experimental epilepsy, MMP and TIMP expression were persistently dysregulated in the hippocampus compared with in controls. IPR-179 treatment reduced seizure severity in the rapid-kindling model and reduced the number of spontaneous seizures in the kainic acid model (during and up to 7 weeks after delivery) without side effects while improving cognitive behavior. Moreover, our data suggest that IPR-179 prevented an MMP2/9-dependent switch-off normally restraining network excitability during the activity period. Since increased MMP expression is a prominent hallmark of the human epileptogenic brain and the MMP inhibitor IPR-179 exhibits antiseizure and antiepileptogenic effects in rodent epilepsy models and attenuates seizure-induced cognitive decline, it deserves further investigation in clinical trials., Introduction Currently, approximately 65 million people worldwide have epilepsy, and temporal lobe epilepsy (TLE) is the most common form in adults (1). Around 30% of patients inadequately respond to the [...]

Published
2021
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20. Author Correction:Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment (Scientific Reports, (2017), 7, 1, (8089), 10.1038/s41598-017-06145-8)

Author

Mills, James D., Iyer, Anand M., van Scheppingen, Jackelien, Bongaarts, Anika, Anink, Jasper J., Janssen, Bart, Zimmer, Till S., Spliet, Wim G., van Rijen, Peter C., Jansen, Floor E., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Kotulska, Katarzyna, Jozwiak, Sergiusz, Jansen, Anna, Lagae, Lieven, Curatolo, Paolo, Kwiatkowski, David J., Pasterkamp, R. Jeroen, Senthilkumar, Ketharini, von Oerthel, Lars, Hoekman, Marco F., Gorter, Jan A., Crino, Peter B., Mühlebner, Angelika, Scicluna, Brendon P., Aronica, Eleonora, Pathology, APH - Aging & Later Life, APH - Mental Health, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Center of Experimental and Molecular Medicine, AII - Infectious diseases, and AII - Inflammatory diseases

Abstract

This Article contains an error in the Acknowledgements section. “This work was supported by European Union’s Seventh Framework Programme (FP7/2007-2013) under the grant agreement no. 602391 (project acronym EPISTOP; A.I., J.v.S., A.M., E.A., F.I., K.K., S.K., A.J., L.L., P.C., D.K.); Epilepsiefonds (WAR 15-05; RJP); European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642881 (ECMED; A.E., J.G.). None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.” should read: “This work was supported by European Union’s Seventh Framework Programme (FP7/2007-2013) under the Grant Agreement no. 602391 (project acronym EPISTOP; A.I., J.v.S., A.M., E.A., F.I., K.K., S.J., A.J., L.L., P.C., D.K.) and partially supported by the Polish Ministerial funds for science (years 2013–2019) for the implementation of international co-financed project (K.K, S.J.); Epilepsiefonds (WAR 15-05; RJP); European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642881 (ECMED; A.E., J.G.). None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.”.

Published
2022

21. Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour

Author

Haglund, Alexander, primary, Zuber, Verena, additional, Yang, Yifei, additional, Abouzeid, Maya, additional, Feleke, Rahel, additional, Ko, Jeong Hun, additional, Nott, Alexi, additional, Babtie, Ann C., additional, Mills, James D., additional, Muhammed, Louwai, additional, Laaniste, Liisi, additional, Gveric, Djordje O., additional, Clode, Daniel, additional, Pagni, Susanna, additional, Bellampalli, Ravishankara, additional, Somani, Alyma, additional, McDade, Karina, additional, Anink, Jasper J., additional, Mesarosova, Lucia, additional, Aronica, Eleonora, additional, Thom, Maria, additional, Sisodiya, Sanjay M., additional, Srivastava, Prashant K., additional, Malhotra, Dheeraj, additional, Bryois, Julien, additional, Bottolo, Leonardo, additional, and Johnson, Michael R., additional

Published
2022
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23. Brain molecular mechanisms in Rasmussen encephalitis

Author

Leitner, Dominique F., primary, Lin, Ziyan, additional, Sawaged, Zacharia, additional, Kanshin, Evgeny, additional, Friedman, Daniel, additional, Devore, Sasha, additional, Ueberheide, Beatrix, additional, Chang, Julia W., additional, Mathern, Gary W., additional, Anink, Jasper J., additional, Aronica, Eleonora, additional, Wisniewski, Thomas, additional, and Devinsky, Orrin, additional

Published
2022
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24. Serotonin receptor expression in hippocampus and temporal cortex of temporal lobe epilepsy patients by postictal generalized electroencephalographic suppression duration

Author

Leitner, Dominique Frances, primary, Devore, Sasha, additional, Laze, Juliana, additional, Friedman, Daniel, additional, Mills, James D., additional, Liu, Yan, additional, Janitz, Michael, additional, Anink, Jasper J., additional, Baayen, Johannes C., additional, Idema, Sander, additional, van Vliet, Erwin Alexander, additional, Diehl, Beate, additional, Scott, Catherine, additional, Thijs, Roland, additional, Nei, Maromi, additional, Askenazi, Manor, additional, Sivathamboo, Shobi, additional, O'Brien, Terence, additional, Wisniewski, Thomas, additional, Thom, Maria, additional, Aronica, Eleonora, additional, Boldrini, Maura, additional, and Devinsky, Orrin, additional

Published
2022
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26. Differentially Expressed miRNAs in Age-Related Neurodegenerative Diseases: A Meta-Analysis

Author

Noronha, Ocana, Mesarosovo, Lucia, Anink, Jasper J., Iyer, Anand, Aronica, Eleonora, Mills, James D., Pathology, APH - Aging & Later Life, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, and Internal Medicine

Subjects
MicroRNAs, Alzheimer Disease, tauopathies, miRNAs, Genetics, synucleinopathies, Humans, Parkinson Disease, amyloidopathies, neurodegenerative diseases, Supranuclear Palsy, Progressive, Genetics (clinical)
Abstract

To date, no neurodegenerative diseases (NDDs) have cures, and the underlying mechanism of their pathogenesis is undetermined. As miRNAs extensively regulate all biological processes and are crucial regulators of healthy brain function, miRNAs differentially expressed in NDDs may provide insight into the factors that contribute to the emergence of protein inclusions and the propagation of deleterious cellular environments. A meta-analysis of miRNAs dysregulated in Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and frontotemporal lobar degeneration (TDP43 variant) was performed to determine if diseases within a proteinopathy have distinct or shared mechanisms of action leading to neuronal death, and if proteinopathies can be classified on the basis of their miRNA profiles. Our results identified both miRNAs distinct to the anatomy, disease type and pathology, and miRNAs consistently dysregulated within single proteinopathies and across neurodegeneration in general. Our results also highlight the necessity to minimize the variability between studies. These findings showcase the need for more transcriptomic research on infrequently occurring NDDs, and the need for the standardization of research techniques and platforms utilized across labs and diseases.

Published
2022
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27. Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways

Author

Blokhuis, Anna M., Koppers, Max, Groen, Ewout J. N., van den Heuvel, Dianne M. A., Dini Modigliani, Stefano, Anink, Jasper J., Fumoto, Katsumi, van Diggelen, Femke, Snelting, Anne, Sodaar, Peter, Verheijen, Bert M., Demmers, Jeroen A. A., Veldink, Jan H., Aronica, Eleonora, Bozzoni, Irene, den Hertog, Jeroen, van den Berg, Leonard H., and Pasterkamp, R. Jeroen

Published
2016
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28. Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment

Author

Mills, James D., Iyer, Anand M., van Scheppingen, Jackelien, Bongaarts, Anika, Anink, Jasper J., Janssen, Bart, Zimmer, Till S., Spliet, Wim G., van Rijen, Peter C., Jansen, Floor E., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Kotulska, Katarzyna, Jozwiak, Sergiusz, Jansen, Anna, Lagae, Lieven, Curatolo, Paolo, Kwiatkowski, David J., Pasterkamp, R. Jeroen, Senthilkumar, Ketharini, von Oerthel, Lars, Hoekman, Marco F., Gorter, Jan A., Crino, Peter B., Mühlebner, Angelika, Scicluna, Brendon P., and Aronica, Eleonora

Published
2017
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29. The Gelatinase Inhibitor ACT-03 Reduces Gliosis in the Rapid Kindling Rat Model of Epilepsy, and Attenuates Inflammation and Loss of Barrier Integrity In Vitro

Author

Broekaart, Diede W. M., primary, Zimmer, Till S., additional, Cohen, Sophie T., additional, Tessers, Rianne, additional, Anink, Jasper J., additional, de Vries, Helga E., additional, Gorter, Jan A., additional, Prades, Roger, additional, Aronica, Eleonora, additional, and van Vliet, Erwin A., additional

Published
2022
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30. Differentially Expressed miRNAs in Age-Related Neurodegenerative Diseases:A Meta-Analysis

Author

Noronha, Ocana, Mesarosovo, Lucia, Anink, Jasper J., Iyer, Anand, Aronica, Eleonora, Mills, James D., Noronha, Ocana, Mesarosovo, Lucia, Anink, Jasper J., Iyer, Anand, Aronica, Eleonora, and Mills, James D.

Abstract

To date, no neurodegenerative diseases (NDDs) have cures, and the underlying mechanism of their pathogenesis is undetermined. As miRNAs extensively regulate all biological processes and are crucial regulators of healthy brain function, miRNAs differentially expressed in NDDs may provide insight into the factors that contribute to the emergence of protein inclusions and the propagation of deleterious cellular environments. A meta-analysis of miRNAs dysregulated in Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and frontotemporal lobar degeneration (TDP43 variant) was performed to determine if diseases within a proteinopathy have distinct or shared mechanisms of action leading to neuronal death, and if proteinopathies can be classified on the basis of their miRNA profiles. Our results identified both miRNAs distinct to the anatomy, disease type and pathology, and miRNAs consistently dysregulated within single proteinopathies and across neurodegeneration in general. Our results also highlight the necessity to minimize the variability between studies. These findings showcase the need for more transcriptomic research on infrequently occurring NDDs, and the need for the standardization of research techniques and platforms utilized across labs and diseases.

Published
2022

31. Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period

Author

Neurologen, Brain, Pathologie Pathologen staf, Cancer, Neurochirurgen, Pathologie, Korotkov, Anatoly, Luinenburg, Mark J, Romagnolo, Alessia, Zimmer, Till S, van Scheppingen, Jackelien, Bongaarts, Anika, Broekaart, Diede W M, Anink, Jasper J, Mijnsbergen, Caroline, Jansen, Floor E, van Hecke, Wim, Spliet, Wim G, van Rijen, Peter C, Feucht, Martha, Hainfellner, Johannes A, Krsek, Pavel, Zamecnik, Josef, Crino, Peter B, Kotulska, Katarzyna, Lagae, Lieven, Jansen, Anna C, Kwiatkowski, David J, Jozwiak, Sergiusz, Curatolo, Paolo, Mühlebner, Angelika, van Vliet, Erwin A, Mills, James D, Aronica, Eleonora, Neurologen, Brain, Pathologie Pathologen staf, Cancer, Neurochirurgen, Pathologie, Korotkov, Anatoly, Luinenburg, Mark J, Romagnolo, Alessia, Zimmer, Till S, van Scheppingen, Jackelien, Bongaarts, Anika, Broekaart, Diede W M, Anink, Jasper J, Mijnsbergen, Caroline, Jansen, Floor E, van Hecke, Wim, Spliet, Wim G, van Rijen, Peter C, Feucht, Martha, Hainfellner, Johannes A, Krsek, Pavel, Zamecnik, Josef, Crino, Peter B, Kotulska, Katarzyna, Lagae, Lieven, Jansen, Anna C, Kwiatkowski, David J, Jozwiak, Sergiusz, Curatolo, Paolo, Mühlebner, Angelika, van Vliet, Erwin A, Mills, James D, and Aronica, Eleonora

Published
2022

32. Increased expression of complement components in tuberous sclerosis complex and focal cortical dysplasia type 2B brain lesions

Author

Neurologen, Brain, Neurochirurgen, Pathologie, Pathologie Pathologen staf, Cancer, Gruber, Victoria-Elisabeth, Luinenburg, Mark J, Colleselli, Katrin, Endmayr, Verena, Anink, Jasper J, Zimmer, Till S, Jansen, Floor, Gosselaar, Peter, Coras, Roland, Scholl, Theresa, Blumcke, Ingmar, Pimentel, José, Hainfellner, Johannes A, Höftberger, Romana, Rössler, Karl, Feucht, Martha, van Scheppingen, Jackelien, Aronica, Eleonora, Mühlebner, Angelika, Neurologen, Brain, Neurochirurgen, Pathologie, Pathologie Pathologen staf, Cancer, Gruber, Victoria-Elisabeth, Luinenburg, Mark J, Colleselli, Katrin, Endmayr, Verena, Anink, Jasper J, Zimmer, Till S, Jansen, Floor, Gosselaar, Peter, Coras, Roland, Scholl, Theresa, Blumcke, Ingmar, Pimentel, José, Hainfellner, Johannes A, Höftberger, Romana, Rössler, Karl, Feucht, Martha, van Scheppingen, Jackelien, Aronica, Eleonora, and Mühlebner, Angelika

Published
2022

33. Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

Author

Neurologen, Brain, Pathologie Pathologen staf, Cancer, Pathologie, Bongaarts, Anika, Mijnsbergen, Caroline, Anink, Jasper J, Jansen, Floor E, Spliet, Wim G M, den Dunnen, Wilfred F A, Coras, Roland, Blümcke, Ingmar, Paulus, Werner, Gruber, Victoria E, Scholl, Theresa, Hainfellner, Johannes A, Feucht, Martha, Kotulska, Katarzyna, Jozwiak, Sergiusz, Grajkowska, Wieslawa, Buccoliero, Anna Maria, Caporalini, Chiara, Giordano, Flavio, Genitori, Lorenzo, Söylemezoğlu, Figen, Pimentel, José, Jones, David T W, Scicluna, Brendon P, Schouten-van Meeteren, Antoinette Y N, Mühlebner, Angelika, Mills, James D, Aronica, Eleonora, Neurologen, Brain, Pathologie Pathologen staf, Cancer, Pathologie, Bongaarts, Anika, Mijnsbergen, Caroline, Anink, Jasper J, Jansen, Floor E, Spliet, Wim G M, den Dunnen, Wilfred F A, Coras, Roland, Blümcke, Ingmar, Paulus, Werner, Gruber, Victoria E, Scholl, Theresa, Hainfellner, Johannes A, Feucht, Martha, Kotulska, Katarzyna, Jozwiak, Sergiusz, Grajkowska, Wieslawa, Buccoliero, Anna Maria, Caporalini, Chiara, Giordano, Flavio, Genitori, Lorenzo, Söylemezoğlu, Figen, Pimentel, José, Jones, David T W, Scicluna, Brendon P, Schouten-van Meeteren, Antoinette Y N, Mühlebner, Angelika, Mills, James D, and Aronica, Eleonora

Published
2022

35. Additional file 2 of Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period

Author

Korotkov, Anatoly, Luinenburg, Mark J., Romagnolo, Alessia, Zimmer, Till S., van Scheppingen, Jackelien, Bongaarts, Anika, Broekaart, Diede W. M., Anink, Jasper J., Mijnsbergen, Caroline, Jansen, Floor E., van Hecke, Wim, Spliet, Wim G., van Rijen, Peter C., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Crino, Peter B., Kotulska, Katarzyna, Lagae, Lieven, Jansen, Anna C., Kwiatkowski, David J., Jozwiak, Sergiusz, Curatolo, Paolo, M��hlebner, Angelika, van Vliet, Erwin A., Mills, James D., and Aronica, Eleonora

Subjects
Data_FILES
Abstract

Additional file 2.

Published
2022
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36. Increased expression of complement components in tuberous sclerosis complex and focal cortical dysplasia type 2B brain lesions

Author

Gruber, Victoria‐Elisabeth, primary, Luinenburg, Mark J., additional, Colleselli, Katrin, additional, Endmayr, Verena, additional, Anink, Jasper J., additional, Zimmer, Till S., additional, Jansen, Floor, additional, Gosselaar, Peter, additional, Coras, Roland, additional, Scholl, Theresa, additional, Blumcke, Ingmar, additional, Pimentel, José, additional, Hainfellner, Johannes A., additional, Höftberger, Romana, additional, Rössler, Karl, additional, Feucht, Martha, additional, Scheppingen, Jackelien, additional, Aronica, Eleonora, additional, and Mühlebner, Angelika, additional

Published
2021
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37. Dysregulation of miR-543 in Parkinson's disease: Impact on the neuroprotective gene SIRT1.

Author

Scheper, Mirte, Iyer, Anand, Anink, Jasper J., Mesarosova, Lucia, Mills, James D., and Aronica, Eleonora

Subjects
PARKINSON'S disease, SIRTUINS, REVERSE transcriptase polymerase chain reaction, WHITE matter (Nerve tissue)
Abstract

Aims: Parkinson's disease (PD) is a progressive and age-dependent neurodegenerative disease characterised clinically by a variety of motor symptoms and cognitive impairment. PD was initially considered to be a grey matter disease; however, recently, evidence has emerged that white matter changes in PD precede the neuronal loss seen in the grey matter. The cause of these initial white matter changes is yet to be elucidated. Here, we explored whether dysregulated miRNAs and their target mRNA could provide insight into the underlying mechanisms of early white matter changes in PD. Methods: We analysed the expression of miRNAs in three different stages of PD through RNA-sequencing and validated the differential expression of miRNAs through quantitative reverse transcription polymerase chain reaction. With bioinformatic analyses, we predicted target genes of dysregulated miRNAs and investigated their biomarker potential. Finally, in vitro, we confirmed the targetting of the gene SIRT1 by miR-543. Results: We identified 12 dysregulated miRNAs in PD and found that miR-543 holds potential as a biomarker for late-stage PD with dementia. We report upregulation of miR-543 in early PD white matter tissue and downregulation of SIRT1. In vitro experiments showed that the upregulation of miR-543 results in the downregulation of SIRT1 in the white matter, but not in the grey matter. Conclusions: We validated SIRT1 as a target of miR-543 in the brain and showed its function as a potential biomarker. Our results highlight the idea that dysregulation of miR-543 in early PD white matter, resulting in the dysregulation of SIRT1, potentially influencing the early white matter changes observed in PD. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Brain molecular mechanisms in Rasmussen encephalitis.

Author

Leitner, Dominique F., Lin, Ziyan, Sawaged, Zacharia, Kanshin, Evgeny, Friedman, Daniel, Devore, Sasha, Ueberheide, Beatrix, Chang, Julia W., Mathern, Gary W., Anink, Jasper J., Aronica, Eleonora, Wisniewski, Thomas, and Devinsky, Orrin

Subjects
EPILEPSY, KILLER cells, ENCEPHALITIS, HLA histocompatibility antigens, FALSE discovery rate, SURGERY
Abstract

Objective: This study was undertaken to identify molecular mechanisms in brain tissue of Rasmussen encephalitis (RE) when compared to people with non‐RE epilepsy (PWE) and control cases using whole exome sequencing (WES), RNAseq, and proteomics. Methods: Frozen brain tissue (ages = 2–19 years) was obtained from control autopsy (n = 14), surgical PWE (n = 10), and surgical RE cases (n = 27). We evaluated WES variants in RE associated with epilepsy, seizures, RE, and human leukocyte antigens (HLAs). Differential expression was evaluated by RNAseq (adjusted p <.05) and label‐free quantitative mass spectrometry (false discovery rate < 5%) in the three groups. Results: WES revealed no common pathogenic variants in RE, but several rare and likely deleterious variants of unknown significance (VUS; ANGPTL7/MTOR, SCN1A, FCGR3B, MTOR) and more common HLA VUS in >25% of RE cases (HLA‐DRB1, HLA‐DQA2), all with allele frequency < 5% in the general population. RNAseq in RE versus PWE (1516 altered transcripts) revealed significant activation of crosstalk between dendritic and natural killer cells (p = 7.94 × 10−6, z = 2.65), in RE versus control (7466 transcripts) neuroinflammation signaling activation (p = 6.31 × 10−13, z = 5.07), and in PWE versus control (945 transcripts) phagosome formation activation (p = 2.00 × 10−13, z = 5.61). Proteomics detected fewer altered targets. Significance: In RE, we identified activated immune signaling pathways and immune cell type annotation enrichment that suggest roles of the innate and adaptive immune responses, as well as HLA variants that may increase vulnerability to RE. Follow‐up studies could evaluate cell type density and subregional localization associated with top targets, clinical history (neuropathology, disease duration), and whether modulating crosstalk between dendritic and natural killer cells may limit disease progression. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

Author

Bongaarts, Anika, primary, Mijnsbergen, Caroline, additional, Anink, Jasper J., additional, Jansen, Floor E., additional, Spliet, Wim G. M., additional, den Dunnen, Wilfred F. A., additional, Coras, Roland, additional, Blümcke, Ingmar, additional, Paulus, Werner, additional, Gruber, Victoria E., additional, Scholl, Theresa, additional, Hainfellner, Johannes A., additional, Feucht, Martha, additional, Kotulska, Katarzyna, additional, Jozwiak, Sergiusz, additional, Grajkowska, Wieslawa, additional, Buccoliero, Anna Maria, additional, Caporalini, Chiara, additional, Giordano, Flavio, additional, Genitori, Lorenzo, additional, Söylemezoğlu, Figen, additional, Pimentel, José, additional, Jones, David T. W., additional, Scicluna, Brendon P., additional, Schouten-van Meeteren, Antoinette Y. N., additional, Mühlebner, Angelika, additional, Mills, James D., additional, and Aronica, Eleonora, additional

Published
2021
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40. Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment.

Author

Mills, James D., Iyer, Anand M., van Scheppingen, Jackelien, Bongaarts, Anika, Anink, Jasper J., Janssen, Bart, Zimmer, Till S., Spliet, Wim G., van Rijen, Peter C., Jansen, Floor E., Feucht, Martha, Hainfellner, Johannes A., Krsek, Pavel, Zamecnik, Josef, Kotulska, Katarzyna, Jozwiak, Sergiusz, Jansen, Anna, Lagae, Lieven, Curatolo, Paolo, and Kwiatkowski, David J.

Subjects
TUBEROUS sclerosis, COMPUTATIONAL complexity, NON-coding RNA, PATHOLOGICAL physiology, AUTOPSY, TUBERS, RNA sequencing, GLUTAMATE receptors
Abstract

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). TSC is associated with autism, intellectual disability and severe epilepsy. Cortical tubers are believed to represent the neuropathological substrates of these disabling manifestations in TSC. In the presented study we used high-throughput RNA sequencing in combination with systems-based computational approaches to investigate the complexity of the TSC molecular network. Overall we detected 438 differentially expressed genes and 991 differentially expressed small non-coding RNAs in cortical tubers compared to autopsy control brain tissue. We observed increased expression of genes associated with inflammatory, innate and adaptive immune responses. In contrast, we observed a down-regulation of genes associated with neurogenesis and glutamate receptor signaling. MicroRNAs represented the largest class of over-expressed small non-coding RNA species in tubers. In particular, our analysis revealed that the miR-34 family (including miR-34a, miR-34b and miR-34c) was significantly over-expressed. Functional studies demonstrated the ability of miR-34b to modulate neurite outgrowth in mouse primary hippocampal neuronal cultures. This study provides new insights into the TSC transcriptomic network along with the identification of potential new treatment targets. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies

Author

Gruber, Victoria‐Elisabeth, primary, Lang, Judith, additional, Endmayr, Verena, additional, Diehm, Robert, additional, Pimpel, Birgit, additional, Glatter, Sarah, additional, Anink, Jasper J., additional, Bongaarts, Anika, additional, Luinenburg, Mark J., additional, Reinten, Roy J., additional, Wel, Nicole, additional, Larsen, Per, additional, Hainfellner, Johannes A., additional, Rössler, Karl, additional, Aronica, Eleonora, additional, Scholl, Theresa, additional, Mühlebner, Angelika, additional, and Feucht, Martha, additional

Published
2021
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42. MicroRNA‐34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis

Author

Korotkov, Anatoly, primary, Sim, Nam Suk, additional, Luinenburg, Mark J., additional, Anink, Jasper J., additional, van Scheppingen, Jackelien, additional, Zimmer, Till S., additional, Bongaarts, Anika, additional, Broekaart, Diede W. M., additional, Mijnsbergen, Caroline, additional, Jansen, Floor E., additional, Van Hecke, Wim, additional, Spliet, Wim G. M., additional, van Rijen, Peter C., additional, Feucht, Martha, additional, Hainfellner, Johannes A., additional, Kršek, Pavel, additional, Zamecnik, Josef, additional, Crino, Peter B., additional, Kotulska, Katarzyna, additional, Lagae, Lieven, additional, Jansen, Anna C., additional, Kwiatkowski, David J., additional, Jozwiak, Sergiusz, additional, Curatolo, Paolo, additional, Mühlebner, Angelika, additional, Lee, Jeong H., additional, Mills, James D., additional, van Vliet, Erwin A., additional, and Aronica, Eleonora, additional

Published
2021
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43. Balloon cells promote immune system activation in focal cortical dysplasia type 2b

Author

Zimmer, Till S., primary, Broekaart, Diede W. M., additional, Luinenburg, Mark, additional, Mijnsbergen, Caroline, additional, Anink, Jasper J., additional, Sim, Nam Suk, additional, Michailidou, Iliana, additional, Jansen, Floor E., additional, Rijen, Peter C., additional, Lee, Jeong Ho, additional, François, Liesbeth, additional, Eyll, Jonathan, additional, Dedeurwaerdere, Stefanie, additional, Vliet, Erwin A., additional, Mühlebner, Angelika, additional, Mills, James D., additional, and Aronica, Eleonora, additional

Published
2021
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44. Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies

Author

Pathologie, Pathologie Pathologen staf, Cancer, Gruber, Victoria-Elisabeth, Lang, Judith, Endmayr, Verena, Diehm, Robert, Pimpel, Birgit, Glatter, Sarah, Anink, Jasper J, Bongaarts, Anika, Luinenburg, Mark J, Reinten, J A, van der Wel, Nicole, Larsen, Per, Hainfellner, Johannes A, Rössler, Karl, Aronica, Eleonora, Scholl, Theresa, Mühlebner, Angelika, Feucht, Martha, Pathologie, Pathologie Pathologen staf, Cancer, Gruber, Victoria-Elisabeth, Lang, Judith, Endmayr, Verena, Diehm, Robert, Pimpel, Birgit, Glatter, Sarah, Anink, Jasper J, Bongaarts, Anika, Luinenburg, Mark J, Reinten, J A, van der Wel, Nicole, Larsen, Per, Hainfellner, Johannes A, Rössler, Karl, Aronica, Eleonora, Scholl, Theresa, Mühlebner, Angelika, and Feucht, Martha

Published
2021

45. Balloon cells promote immune system activation in focal cortical dysplasia type 2B

Author

Neurologen, Brain, Neurochirurgen, Pathologie Pathologen staf, Cancer, Pathologie, Zimmer, Till S, Broekaart, Diede W M, Luinenburg, Mark, Mijnsbergen, Caroline, Anink, Jasper J, Sim, Nam Suk, Michailidou, Iliana, Jansen, Floor E, van Rijen, Peter C, Lee, Jeong Ho, François, Liesbeth, van Eyll, Jonathan, Dedeurwaerdere, Stefanie, van Vliet, Erwin A, Mühlebner, Angelika, Mills, James D, Aronica, Eleonora, Neurologen, Brain, Neurochirurgen, Pathologie Pathologen staf, Cancer, Pathologie, Zimmer, Till S, Broekaart, Diede W M, Luinenburg, Mark, Mijnsbergen, Caroline, Anink, Jasper J, Sim, Nam Suk, Michailidou, Iliana, Jansen, Floor E, van Rijen, Peter C, Lee, Jeong Ho, François, Liesbeth, van Eyll, Jonathan, Dedeurwaerdere, Stefanie, van Vliet, Erwin A, Mühlebner, Angelika, Mills, James D, and Aronica, Eleonora

Published
2021

48. Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients

Author

Leitner, Dominique F., primary, Mills, James D., additional, Pires, Geoffrey, additional, Faustin, Arline, additional, Drummond, Eleanor, additional, Kanshin, Evgeny, additional, Nayak, Shruti, additional, Askenazi, Manor, additional, Verducci, Chloe, additional, Chen, Bei Jun, additional, Janitz, Michael, additional, Anink, Jasper J., additional, Baayen, Johannes C., additional, Idema, Sander, additional, van Vliet, Erwin A., additional, Devore, Sasha, additional, Friedman, Daniel, additional, Diehl, Beate, additional, Scott, Catherine, additional, Thijs, Roland, additional, Wisniewski, Thomas, additional, Ueberheide, Beatrix, additional, Thom, Maria, additional, Aronica, Eleonora, additional, and Devinsky, Orrin, additional

Published
2021
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49. Increased expression of miR142 and miR155 in glial and immune cells after traumatic brain injury may contribute to neuroinflammation via astrocyte activation

Author

Korotkov, Anatoly, Puhakka, Noora, Gupta, Shalini Das, Vuokila, Niina, Broekaart, Diede W M, Anink, Jasper J, Heiskanen, Mette, Karttunen, Jenni, van Scheppingen, Jackelien, Huitinga, Inge, Mills, James D, van Vliet, Erwin A, Pitkänen, Asla, Aronica, Eleonora, Korotkov, Anatoly, Puhakka, Noora, Gupta, Shalini Das, Vuokila, Niina, Broekaart, Diede W M, Anink, Jasper J, Heiskanen, Mette, Karttunen, Jenni, van Scheppingen, Jackelien, Huitinga, Inge, Mills, James D, van Vliet, Erwin A, Pitkänen, Asla, and Aronica, Eleonora

Abstract

Traumatic brain injury (TBI) is associated with the pathological activation of immune-competent cells in the brain, such as astrocytes, microglia, and infiltrating immune blood cells, resulting in chronic inflammation and gliosis. This may contribute to the secondary injury after TBI, thus understanding of these processes is crucial for the development of effective treatments of post-traumatic pathologies. MicroRNAs (miRNAs, miRs) are small non-coding RNAs, functioning as post-transcriptional regulators of gene expression. The increased expression of inflammation-associated microRNAs miR155 and miR142 has been reported after TBI in rats. However, expression of these miRNAs in the human brain post-TBI is not studied and their functions are not well understood. Moreover, circulating miR155 and miR142 are candidate biomarkers. Therefore, we characterized miR142 and miR155 expression in the perilesional cortex and plasma of rats that underwent lateral fluid-percussion injury, a model for TBI, and in the human perilesional cortex post-TBI. We demonstrated higher miR155 and miR142 expression in the perilesional cortex of rats 2 weeks post-TBI. In plasma, miR155 was associated with proteins and miR142 with extracellular vesicles, however their expression did not change. In the human perilesional cortex miR155 was most prominently expressed by activated astrocytes, whereas miR142 was expressed predominantly by microglia, macrophages and lymphocytes. Pro-inflammatory medium from macrophage-like cells stimulated miR155 expression in astrocytes and overexpression of miR142 in these cells further potentiated a pro-inflammatory state of activated astrocytes. We conclude that miR155 and miR142 promote brain inflammation via astrocyte activation and may be involved in the secondary brain injury after TBI.

Published
2020

50. The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas

Author

ZL Kinder Ner en Nec Medisch, Brain, Pathologie mortuarium en obductie, Pathologie Pathologen staf, Cancer, Pathologie Opleiding, Pathologie, Bongaarts, Anika, van Scheppingen, Jackelien, Korotkov, Anatoly, Mijnsbergen, Caroline, Anink, Jasper J., Jansen, Floor E., Spliet, Wim G.M., den Dunnen, Wilfred F.A., Gruber, Victoria E., Scholl, Theresa, Samueli, Sharon, Hainfellner, Johannes A., Feucht, Martha, Kotulska, Katarzyna, Jozwiak, Sergiusz, Grajkowska, Wieslawa, Buccoliero, Anna Maria, Caporalini, Chiara, Giordano, Flavio, Genitori, Lorenzo, Coras, Roland, Blümcke, Ingmar, Krsek, Pavel, Zamecnik, Josef, Meijer, Lisethe, Scicluna, Brendon P., Schouten-van Meeteren, Antoinette Y.N., Mühlebner, Angelika, Mills, James D., Aronica, Eleonora, ZL Kinder Ner en Nec Medisch, Brain, Pathologie mortuarium en obductie, Pathologie Pathologen staf, Cancer, Pathologie Opleiding, Pathologie, Bongaarts, Anika, van Scheppingen, Jackelien, Korotkov, Anatoly, Mijnsbergen, Caroline, Anink, Jasper J., Jansen, Floor E., Spliet, Wim G.M., den Dunnen, Wilfred F.A., Gruber, Victoria E., Scholl, Theresa, Samueli, Sharon, Hainfellner, Johannes A., Feucht, Martha, Kotulska, Katarzyna, Jozwiak, Sergiusz, Grajkowska, Wieslawa, Buccoliero, Anna Maria, Caporalini, Chiara, Giordano, Flavio, Genitori, Lorenzo, Coras, Roland, Blümcke, Ingmar, Krsek, Pavel, Zamecnik, Josef, Meijer, Lisethe, Scicluna, Brendon P., Schouten-van Meeteren, Antoinette Y.N., Mühlebner, Angelika, Mills, James D., and Aronica, Eleonora

Published
2020

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