1. Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection
- Author
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Shun Li, Florian olde Heuvel, Rida Rehman, Oumayma Aousji, Albrecht Froehlich, Zhenghui Li, Rebecca Jark, Wanhong Zhang, Alison Conquest, Sarah Woelfle, Michael Schoen, Caitlin C. O´Meara, Richard Lee Reinhardt, David Voehringer, Jan Kassubek, Albert Ludolph, Markus Huber-Lang, Bernd Knöll, Maria Cristina Morganti-Kossmann, Marisa M. Brockmann, Tobias Boeckers, and Francesco Roselli
- Subjects
Male ,Multidisciplinary ,metabolism [Interleukin-13] ,genetics [Brain Injuries, Traumatic] ,General Physics and Astronomy ,General Chemistry ,metabolism [Brain Injuries, Traumatic] ,genetics [Interleukin-13] ,General Biochemistry, Genetics and Molecular Biology ,Neuroprotection ,Rats ,Mice ,metabolism [Neurons] ,Animals ,Humans ,physiology [Neuronal Plasticity] ,ddc:500 - Abstract
Immune system molecules are expressed by neurons, yet their functions are often unknown. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, and human brains, whose engagement upregulates the phosphorylation of NMDAR and AMPAR subunits and, in turn, increases synaptic activity and CREB-mediated transcription. We demonstrate that increased IL-13 is a hallmark of traumatic brain injury (TBI) in male mice as well as in two distinct cohorts of human patients. We also provide evidence that IL-13 upregulation protects neurons from excitotoxic death. We show IL-13 upregulation occurring in several cohorts of human brain samples and in cerebrospinal fluid (CSF). Thus, IL-13 is a physiological modulator of synaptic physiology of neuronal origin, with implications for the establishment of synaptic plasticity and the survival of neurons under injury conditions. Furthermore, we suggest that the neuroprotection afforded through the upregulation of IL-13 represents an entry point for interventions in the pathophysiology of TBI.
- Published
- 2023