Gostujuće predavanje prof. dr Jelene Radulović – SANU, 25.10.2024.

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Obaveštavamo vas o promeni mesta održavanja gostujućeg predavanja Prof. dr Jelene Radulović pod nazivom “Memory formation through DNA sensing”. Predavanje će se održati u Svečanoj sali SANU, 25.10.2024. od 14h.

Prof. dr Jelena Radulović radi na Medicinskom Fakultetu Albert Ajnštajn u Njujorku, SAD, i Aarhus Univerzitetu u Danskoj.

Sa zadovoljstvom vas pozivamo da čujete predavanje čiji kratak opis, kao i biografiju naše uvažene gošće, možete pročitati u nastavku mejla.

Kratka Biografija

Short Bio

Jelena Radulovic, Laboratorija za izucavanje neurobiologije stresa i memorije

(The Neurobiology of Stress-Related Memories: Basic and Translational Perspective)

Jelena Radulovic graduated at the School of Medicine, University of Belgrade, Serbia, in 1987 and completed her PhD thesis in 1993, at the same University. In 1996, she moved to the Max Planck Institute for Experimental Medicine, Goettingen, Germany, as a postdoctoral fellow and subsequently as a group leader at the Department of Molecular Neuroendocrinology. From 2004-2020 she has been with Northwestern University as the Dunbar Professor of Bipolar Disease in the Department of Psychiatry and Behavioral Sciences. She is currently the Sylvia and Robert S. Olnick Professor of Neuroscience and Professor of Psychiatry and Behavioral Sciences at Albert Einstein College of Medicine, NY, where she also serves as the Director of the Psychiatry Institute Montefiore Einstein (PRIME). She is also a Lundbeck Professor at Aarhus University, where she leads a laboratory at the Department of Biomedicine. Her long-standing research focus has been on the neurobiological mechanisms by which stressful experiences shape memory circuits and contribute to maladaptive behaviors in preclinical models.  She has published over 130 papers, many in top-tier journals (Nature Genetics, 2000, Nature Neuroscuience 2013, 2015, 2019, Nature, 2024) and serves as advisor and reviewer at prestigious national and international boards in the USA, Denmark, The Netherlands, France, UK, Austria, China, etc.). She is a member of the Society for Neuroscience and a council member of the Molecular and Cellular Cognition Society.

Abstract

As hippocampal neurons respond to diverse types of information¹, a subset assembles into microcircuits representing a memory². Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage^3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes⁶. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.

1. McKenzie, S. et al. Hippocampal representation of related and opposing memories develop within distinct, hierarchically organized neural schemas. Neuron 83, 202–215 (2014).

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2. Terada, S. et al. Adaptive stimulus selection for consolidation in the hippocampus. Nature601, 240–244 (2022).

Article ADS CAS PubMed Google Scholar 

3. Crowe, S. L., Movsesyan, V. A., Jorgensen, T. J. & Kondratyev, A. Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation. Eur. J. Neurosci. 23, 2351–2361 (2006).

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4. Suberbielle, E. et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. Nat. Neurosci. 16, 613–621 (2013).

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5. Madabhushi, R. et al. Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161, 1592–1605 (2015).

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6. Mullee, L. I. & Morrison, C. G. Centrosomes in the DNA damage response—the hub outside the centre. Chromosome Res. 24, 35–51 (2016).

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