Biomedicine Seminar

Lecturer: Jelena Radulovic - Title: Neuronal Immune Signaling and Memory Functions

Oplysninger om arrangementet

Tidspunkt

Onsdag 3. september 2025,  kl. 12:00 - 13:00

Sted

Lille anatomisk (1231-424)

During memory formation, hippocampal neurons undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage. We demonstrated that in discrete clusters of excitatory hippocampal CA1 neurons, learning-induced changes involve an extended transcriptional program initiated by persistent double-stranded DNA (dsDNA) breaks. Occasionally, when nuclear envelopes rupture, histone and dsDNA fragments are released in the adjacent endoplasmic reticulum. Following these early events, some neurons acquire an inflammatory phenotype involving activation of TLR9 signaling and accumulation of centrosomal DNA damage repair complexes. These processes were restricted to neurons and, surprisingly, did not involve cell types (astrocytes or microglia) typically associated with inflammation. Neuron-specific knockdown of Tlr9 impaired memory and prevented the development of neuron-specific inflammatory phenotype. In addition, TLR9 was required for DNA damage repair, ciliogenesis and build-up of perineuronal nets, transforming initially molecular events to structural changes associated with memory. Disrupting the neuronal TLR9 inflammatory signaling induced genomic instability, revealing an essential function of immune signaling in neuronal integrity. Immplications of the findings for memory-related neuronal functions and neuronal health are discussed.