Rxivist logo

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

By Andre Altmann, Mina Ryten, Martina Di Nunzio, Teresa Ravizza, Daniele Tolomeo, Regina H. Reynolds, Alyma Somani, Marco Bacigaluppi, Valentina Iori, Edoardo Micotti, Juan A. Botía, Julie Absil, Saud Alhusaini, Marina K. M. Alvim, Pia Auvinen, Nuria Bargallo, Emanuele Bartolini, Benjamin Bender, Felipe P. G. Bergo, Tauana Bernardes, Andrea Bernasconi, Neda Bernasconi, Boris C. Bernhardt, Karen Blackmon, Barbara Braga, Maria Eugenia Caligiuri, Anna Calvo, Chad Carlson, Sarah J. Carr, Gianpiero L Cavalleri, Fernando Cendes, Jian Chen, Shuai Chen, Andrea Cherubini, Luis Concha, Philippe David, Norman Delanty, Chantal Depondt, Orrin Devinsky, Colin P Doherty, Martin Domin, Niels K Focke, Sonya Foley, Wendy Franca, Antonio Gambardella, Renzo Guerrini, Khalid Hamandi, Derrek P. Hibar, Dmitry Isaev, Graeme D. Jackson, Neda Jahanshad, Reetta Kalviainen, Simon S Keller, Peter Kochunov, Raviteja Kotikalapudi, Magdalena A Kowalczyk, Ruben Kuzniecky, Patrick Kwan, Angelo Labate, Soenke Langner, Matteo Lenge, Min Liu, Pascal Martin, Mario Mascalchi, Stefano Meletti, Marcia E Morita, Terence J O’Brien, Jose C Pariente, Mark P Richardson, Raul Rodriguez-Cruces, Christian Rummel, Taavi Saavalainen, Mira K Semmelroch, Mariasavina Severino, Pasquale Striano, Thomas Thesen, Rhys H Thomas, Manuela Tondelli, Domenico Tortora, Anna Elisabetta Vaudano, Lucy Vivash, Felix von Podewils, Jan Wagner, Bernd Weber, Roland Wiest, Clarissa L. Yasuda, Guohao Zhang, Junsong Zhang, ENIGMA-Epilepsy Working Group, Costin Leu, Andreja Avbersek, EpiPGX Consortium, Maria Thorn, Christopher D. Whelan, Paul Thompson, Carrie McDonald, Annamaria Vezzani, Sanjay M Sisodiya

Posted 14 Nov 2018
bioRxiv DOI: 10.1101/470518

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Download data

  • Downloaded 649 times
  • Download rankings, all-time:
    • Site-wide: 25,901 out of 100,904
    • In neuroscience: 4,314 out of 17,983
  • Year to date:
    • Site-wide: 40,734 out of 100,904
  • Since beginning of last month:
    • Site-wide: 39,752 out of 100,904

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!