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Oral presentation
T28

Chronic IL-1-induced DNA double-strand break response in hippocampal neurons drives cognitive deficits upon latent T. gondii infection

Appointment

Date: Mo, 27/05/2024

Time: 16:45 – 17:00

Talk time: 12 Min.

Discussion time: 3 Min.

Location / Stream:

Goethe-Saal & Galerie

Session

Session IV: Immunology

Topic

Immunology of Acute & Chronic Infection

Authors

Dr. Marcy Belloy (Toulouse / FR), Dr. Benjamin Schmitt (Toulouse / FR), Dr. Florent Marty (Toulouse / FR), Charlotte Paut (Toulouse / FR), Emilie Bassot-Parra (Toulouse / FR), Amel Aïda (Toulouse / FR), Marine Alis (Toulouse / FR), Romain Ecalard (Toulouse / FR), Dr. Raphaël Boursereau (Toulouse / FR), Dr. Daniel Gonzalez-Dunia (Toulouse / FR), Professor Nicolas Blanchard (Toulouse / FR), Dr. Elsa Suberbielle (Toulouse / FR)

Abstract

Chronic inflammation characterized by increased cytokine levels, such as interleukin-1 (IL-1), accompanies many neurological diseases but little is known about IL-1 contribution to cognitive impairment and its interplay with epigenetic processes, including the DNA double-strand break (DSB) response.

Here, we demonstrate that H2A.X-dependent DSB signaling in hippocampal neurons drives cognitive deficits upon chronically elevated IL-1. Mice persistently and latently infected with Toxoplasma gondii display impaired spatial memory consolidation along with elevated IL-1β in the hippocampus. We find that neuronal IL-1 signaling in excitatory neurons is required for the spatial memory deficits caused by T. gondii infection and by chronic systemic infusion of IL-1β. In both cases, the deficit in spatial memory was prevented by the abrogation of neuronal H2A.X-dependent signaling. Our results highlight the instrumental role of cytokine-induced DSB-dependent signaling in spatial memory defects. This novel pathological mechanism in inflammation control of neuronal function may extend to several neurological diseases.