NeuroCoG Seminar Series: Claudia Bagni, Department of Fundamental Neurosciences, University of Lausanne, Suisse

on the February 21, 2020

11:00am to 1:00pm
Molecular mechanisms of social competence

Organized by Frédéric Saudou
Grenoble Institut Neurosciences
On February 21, 2020, NeuroCoG invited Claudia Bagni, Director of the Department of Fundamental Neurosciences, University of Lausanne, Eric Peyrin (Department of Biochimie Molleculaire, Université Grenoble France) and Olivier Moreaud (Neurologue, LPNC) for three conferences at Grenoble Institut Neurosciences (GIN).


Program

11am-12am
Claudia
BAGNI
PhD & Director of the Department of Fundamental Neurosciences, University of Lausanne, Switzerland
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy
Molecular mecanisms of social competence

12am-12.30am
Eric
PEYRIN
Professeur, Department of Pharmacochimie Moléculaire,
Université Grenoble Alpes
Selection of Tau protein-binding DNA aptamers by using the capillary electrophoresis partitioning technique.

12.30am-1pm
Olivier
MOREAUD
Neurologue
CMRR (Centre Mémoire de Ressource et de Recherche) Grenoble Arc Alpin
I don’t understand the word but I know the concept: semantic dementia is not always what it seems

1pm
Buffet

Claudia Bagni

 

PhD & Director of the Department of Fundamental Neurosciences, University of Lausanne, Switzerland
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy


Molecular mechanisms of social competence


Abstract

Individuals with the 15q11.2 microdeletions, which include the CYFIP1 gene, can present with a diverse array of symptoms such as neurobehavioral disturbances, epilepsy and psychiatric problems. The core behavioral features and the underlying molecular mechanisms of this genetic condition, however, remain unclear. In brain, CYFIP1 regulates synapse structure and plasticity by orchestrating at last two processes: actin remodeling and protein synthesis. I will discuss how Cyfip1 haploinsufficiency causes deficits in functional brain connectivity and behaviour and the molecular and cellular mechanisms underlying those deficits. Finally, I will discuss the importance of our findings for other neurodevelopmental disorders.
 

Eric Peyrin

 

Professeur, Department of Pharmacochimie Moléculaire,
Université Grenoble Alpes


Selection of Tau protein-binding DNA aptamers by using the capillary electrophoresis partitioning technique.

(Eric Peyrin, Emmanuelle Fiore, Corinne Ravelet)

Abstract
Numerous analytical methods have been described to detect Alzheimer’s disease (AD) biomarkers in biological fluids. The established approaches are based on the immunoassay principles with a variety of signaling techniques ranging from conventional ELISA-derived systems to emerging sensing platforms based on electrochemical, optical, and piezoelectric transduction [1]. However, immunological methods suffer from a number of drawbacks including the analysis cost and the difficulty of standardization and the assay interferences. In this context, recent research efforts have focused on the development of alternative, biomimetic recognition elements such as peptides, molecular imprinting polymers, and nucleic acid aptamers. While aptamers have stimulated growing interest in both diagnostics and therapy, up to now only a few works have been performed in the development of functional oligonucleotides specific to AD markers. The reported aptamers mainly target the amyloid peptides whereas only one RNA aptamer has been described for the human tau (?) protein [2].
Herein, we will discuss on the isolation of DNA aptamers directed against the whole ? protein by an approach based on the capillary electrophoresis partitioning technique [3]. Isolation of high-affinity DNA sequences towards the target was achieved in only three rounds and one working day (vs 10-20 rounds and several working weeks with conventional SELEX approaches). High-throughput sequencing was next performed and the recognition ability of five selected aptamers was evaluated by surface plasmon resonance using the protein target immobilized on the chip. Finally, the analytical potential of the most affine aptamer was demonstrated through the design of a homogeneous-phase fluorescence anisotropy assay. This DNA aptamer recognizes not only the whole ?-441 but also the ?-381, ?-352, ?-383 isoforms. The sensing platform allows the determination of these targets with a detection limit in the nanomolar range.
References
[1] S. Scarano, S. Lisi, C. Ravelet, E. Peyrin, M. Minunni, Detecting Alzheimer's disease biomarkers: From antibodies to new bio-mimetic receptors and their application to established and emerging bioanalytical platforms - A critical review, Anal. Chim. Acta 940, 21-37, 2016
[2] J.H. Kim, E. Kim, W.H. Choi, J. Lee, J.H. Lee, H. Lee, D.E. Kim, Y.H. Suh, M.J. Lee, Inhibitory RNA Aptamers of Tau Oligomerization and Their Neuroprotective Roles against Proteotoxic Stress, Mol. Pharm. 13, 2039-2048, 2016
[3] S. Lisi, E. Fiore, S. Scarano, E. Pascale, Y. Boehman, F. Ducongé, S. Chierici, M. Minunni, E. Peyrin, C. Ravelet Non-SELEX isolation of DNA aptamers for the homogeneous-phase fluorescence anisotropy sensing of tau Proteins, Anal. Chim. Acta 1038, 173-181, 2018


Olivier Moreaud


Neurologue
CMRR (Centre Mémoire de Ressource et de Recherche) Grenoble Arc Alpin
Thèmes de recherche : Neuropsychologie (maladie d’Alzheimer, aphasie progressive, démence sémantique, mémoire sémantique, mémoire de travail)

I don’t understand the word but I know the concept: semantic dementia is not always what it seems

Abstract
Semantic dementia (SD) is a rare neurodegenerative disease affecting temporal lobes, characterized by a progressive loss of semantic knowledge. Typically, patients lose their ability to identify objects and people, be they in the presence of the real object or person, or seeing a picture of it, or hearing or reading its name. For example, when seeing the picture of a giraffe, a patient will only be able to access general information (usually that it’s an animal, sometimes that it’s a mammal) and he will pretend that he has never seen it before, and similarly, the name “giraffe” will not activate any information other than “I don’t know”. For several reasons, impairment is more marked with names than with pictures, and it is the rule that SD patients, at onset, manifest a relatively preserved access to semantic knowledge from pictures, before a more generalized impairment appears. However, we encountered a few patients that did not develop global semantic impairment during the entire course of their disease, the deficit remaining restricted to the verbal modality. What is striking in these patients is that not only they do not comprehend names but they also cannot access the name when presented with a picture, despite preserved access to semantic knowledge from the picture. Our hypothesis is that these patients do not have a deficit of semantics, but, according to computational models of identification and naming, that they progressively lose their verbal lexicon. We will show differences in retrieval of post semantic knowledge (lexical decision, gender decision) in typical SD patients and atypical, lexical patients, that support this hypothesis.

 


Published on February 26, 2020

Practical informations

Contacts

Sylvie Perrier, chargée de projet et de communication NeuroCoG
sylvie.perrier@univ-grenoble-alpes.fr

Lieu(x)


Grenoble Institut Neurosciences
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