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Linda Tirou, Mariagiovanna Russo, Hélène Faure, Giuliana Pellegrino, Clément Demongin, Mathieu Daynac, Ariane Sharif, Jeremy Amosse, Soazig Le Lay, Raphaël Denis, Serge Luquet, Mohammed Taouis, Yacir Benomar, Martial Ruat

Sonic Hedgehog receptor Patched deficiency in astrocytes enhances glucose metabolism in mice

Molecular Metabolism, 2021, 26 January. doi: 10.1016/j.molmet.2021.101172

Astrocytes are glial cells proposed as the main Sonic Hedgehog (Shh)-responsive cells in the adult brain. Their roles in mediating Shh functions are still poorly understood. In the hypothalamus, astrocytes support neuronal circuits implicated in the regulation of energy metabolism. Here, we investigated the impact of genetic activation of Shh signaling on hypothalamic astrocytes and characterized its effects on energy metabolism.

Mehdi Belmaati Cherkaoui, Ophélie Vacca, Charlotte Izabelle, Anne‐Cécile Boulay, Claire Boulogne, Cynthia Gillet, Jean‐Vianney Barnier, Alvaro Rendon, Martine Cohen‐Salmon, Cyrille Vaillend

Dp71 contribution to the molecular scaffold anchoring aquaporine-4 channels in brain macroglial cells

Glia 2020, 28 November. doi: 10.1002/glia.23941

Intellectual disability in Duchenne muscular dystrophy has been associated with the loss of dystrophin‐protein 71, Dp71, the main dystrophin‐gene product in the adult brain. Dp71 shows major expression in perivascular macroglial endfeet, suggesting that dysfunctional glial mechanisms contribute to cognitive impairments. In the present study, we investigated the molecular alterations induced by a selective loss of Dp71 in mice, using semi‐quantitative immunogold analyses in electron microscopy and immunofluorescence confocal analyses in brain sections and purified gliovascular units. In macroglial pericapillary endfeet of the cerebellum and hippocampus, we found a drastic reduction (70%) of the polarized distribution of aquaporin‐4 (AQP4) channels, a 50% reduction of β‐dystroglycan, and a complete loss of α1‐syntrophin. Interestingly, in the hippocampus and cortex, these effects were not homogeneous: AQP4 and AQP4ex isoforms were mostly lost around capillaries but preserved in large vessels corresponding to pial arteries, penetrating cortical arterioles, and arterioles of the hippocampal fissure, indicating the presence of Dp71‐independent pools of AQP4 in these vascular structures. In conclusion, the depletion of Dp71 strongly alters the distribution of AQP4 selectively in macroglial perivascular endfeet surrounding capillaries. This effect likely affects water homeostasis and blood–brain barrier functions and may thus contribute to the synaptic and cognitive defects associated with Dp71 deficiency.

Coralie Hérent , Séverine Diem, Gilles Fortin , Julien Bouvier

Absent phasing of respiratory and locomotor rhythms in running mice

Elife 2020. 9:e61919 doi: 10.7554/eLife.61919

Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and imposed by a synchronization of breaths to strides is still unclear. Here, we examined respiratory changes during running in the resourceful mouse model. We show that, for a wide range of trotting speeds on a treadmill, respiratory rate increases to a fixed and stable value irrespective of trotting velocities. Respiratory rate was yet further increased during escape-like running and most particularly at gallop. However, we found no temporal coordination of breaths to strides at any speed, intensity, or gait. Our work thus highlights that exercise hyperpnoea can operate, at least in mice and in the presently examined running regimes, without phasic constraints from limb movements.

PubMed or Website : Elife, 1 décembre 2020
Flaria El-Khoury, Jérôme Bignon, Jean-René Martin

Un nouveau petit ARN nucléolaire humain impliqué dans le contrôle de la prolifération cellulaire, jouvence

jouvence, a new human snoRNA involved in the control of cell proliferation. BMC Genomics 21, 817 (2020). doi: 10.1186/s12864-020-07197-3

Les petits ARNs nucléolaires (snoRNAs) sont des ARN-non-codant conservés des archaebactéries au mammifères. Ils sont associés, dans le nucléole, avec des protéines pour former les ribonucléoprotéines. Ils sont subdivisés en deux catégories, les boîtes C/D et les boîtes H/ACA, et servent généralement à modifier les ARN-ribosomaux. Les boîtes H/ACA convertissent l’uridine en pseudouridine. Chez l’humain, certaines pathologies ont été associées à des snoRNAs, alors que plusieurs snoRNAs ont été impliqués dans différents cancers. Récemment, l’équipe de Jean-René Martin (NeuroPSI) a identifié, chez la Drosophile, un nouveau snoRNA, nommé jouvence, et montré que ce dernier, requis dans l’épithélium de l’intestin, est impliqué dans la détermination de la durée de vie. Sa surexpression augmente la durée de vie et protège contre les effect délétères dus au vieillissement, dont notamment les lesions neurodégératives. Comme les snoRNAs sont très conservés au cours de l’évolution, tant structurellement que fonctionnellement, l’orthologue de jouvence a été identifié chez l’humain (il n’était pas annoté dans le génome).

PubMed or Website : BMC Genomics, 23 novembre 2020
Maryline Blin, Julien Fumey, Camille Lejeune, Maxime Policarpo, Julien Leclercq, Stéphane Père, Jorge Torres-Paz, Constance Pierre, Boudjema Imarazene, Sylvie Rétaux

Diversity of olfactory responses and skills in Astyanax mexicanus cavefish populations inhabiting different caves

Diversity 2020, 12(10), 395. doi: 10.3390/d12100395

Understanding the mechanisms of behavioral and sensory adaptation to a novel environement is at stakes both for evolutionary biology and for conservation biology. In an article published in Diversity, researchers of the NeuroPSI Institute have evaluated the olfactory skills of different populations of blind cavefish. Indeed, animals in many phyla are adapted to and thrive in the constant darkness of subterranean environments. To do so, cave animals have presumably evolved mechano- and chemosensory compensations to the loss of vision, as is the case for the blind characiform cavefish, Astyanax mexicanus. Here, we systematically assessed the olfactory capacities of cavefish and surface fish of this species in the lab as well as in the wild, in five different caves in northeastern Mexico. We have used an olfactory setup specially developed to test and record olfactory responses, during fieldwork. Overall cavefish showed lower (i.e., better) olfactory detection thresholds than surface fish. However, wild adult cavefish from the Pachón, Sabinos, Tinaja, Chica and Subterráneo caves showed highly variable responses to the three different odorant molecules they were exposed to. Pachón and Subterráneo cavefish showed the highest olfactory capacities, and Chica cavefish showed no response to the odors presented. We discuss these data, gathered during a special effort in field work in the past five years, with regard to the environmental conditions in which these different cavefish populations live. Our experiments in natural settings document the diversity of cave environments inhabited by a single species of cavefish, A. mexicanus, and highlight the complexity of the plastic and genetic mechanisms that underlie cave adaptation.

PubMed or Website : Diversity, 13 octobre 2020
Bartosz Telenczuk, Maria Telenczuk, Alain Destexhe

Une nouvelle méthode de calcul des signaux électriques cérébraux

A kernel-based method to calculate local field potentials from networks of spiking neurons. Journal of Neuroscience Methods, October 01, 2020. 344:108871. doi: 10.1016/j.jneumeth.2020.108871

Les chercheurs de l'EITN de NeuroPSI ont publié récemment un article dans le Journal of Neuroscience Methods qui propose une nouvelle méthode de calcul des signaux électriques cérébraux. Cette méthode, appelée "Kernel method", permet de calculer les potentiels électriques profonds (Local Field Potential ou LFP) et en surface (Electrocorticogramme ou EcoG) à partir de l’activité des neurones excitateurs et inhibiteurs. Cette méthode se base sur une étude précédente (Telenczuk et al. Scientific Reports 2017), ou les auteurs ont déterminé la relation statistique entre les signaux cérébraux et l’activité des neurones excitateurs et inhibiteurs chez des sujets humains. En reprenant le noyau ("kernel") de cette relation, il est donc possible de calculer ces signaux à partir de la connaissance de l’activité des neurones. Cette méthode sera intégrée dans l'infrastructure EBRAINS du Human Brain Project, pour permettre le calcul de signaux tels que l'EcoG à partir de simulations de parties du cerveau humain. A terme, elle devrait aussi permettre d'envisager le "problème inverse" d'estimer l’activité neuronale à partir de signaux tels que l'EcoG, ce qui représente une perspective intéressante pour l'imagerie de l’activité neuronale chez l'homme.

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