C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain
Abstract
Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer’s disease reduced local amyloid-β amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (33)
Gerard Crowley
Minjung Kim
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Nathanael O’Neill
Research Department of Epilepsy, Queen Square Institute of Neurology, University College London, London, UK.
Emir Turkes
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Fateme Ghasemi
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Luca Giudice
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Sebastiaan De Schepper
Benjy J. Y. Tan
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Benito Maffei
Research Department of Epilepsy, Queen Square Institute of Neurology, University College London, London, UK.
Laís S. S. Ferreira
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Julie Rebejac
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Javier Rueda-Carrasco
Margarita Toneva
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
John Christian Fajardo
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Judy Z. Ge
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Zhengyue Grace Yang
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Paula Korhonen
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Phillip Muckett
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Damaris Bennett
The Francis Crick Institute, London, UK.
Camille Paoletti
UK Dementia Research Institute, Institute of Neurology, University College London, London, UK.
Tammie T. M. Sow
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
David A. Posner
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Annerieke Sierksma
Dimitra Sokolova
Viktoras Konstantellos
Leen Ali
Brain and Systems Immunology Laboratory, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Kiavash Movahedi
Andrew F. MacAskill
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Victor L. J. Tybulewicz
The Francis Crick Institute, London, UK.
Tarja Malm
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Gabriele Lignani
Research Department of Epilepsy, Queen Square Institute of Neurology, University College London, London, UK.
Menna R. Clatworthy
Soyon Hong