Somatosensory and auditory systems support tactile frequency discrimination

OBJECTIF - OBJECTIVE

Auditory scene analysis is essential to many daily activities in which several senses are involved: understanding speech in noise, localization of sounds, musical perception, etc. For example, when a violinist plays a note, the instrument produced sounds and vibrations which activates hearing and tactile systems. Understanding how the brain recruits each of these senses and how they interact with each other remains a matter of study. To better understand tactile perception, the study of neuroanatomical correlates is necessary via low-level perceptual tasks. The main goal of this study was to investigate neural correlates of tactile perception during a simple frequency (pitch) discrimination task via the tactile modality only (no auditory perception). We hypothesized that both somatosensory and auditory cortices will be recruited during the frequency discrimination task even if no sounds were directly presented to the auditory system.

MÉTHODES - METHODS

During the EEG recordings, using an oddball paradigm, tactile stimulation was delivered to 20 healthy participants through a left hand vibrotactile stimulation glove. The paradigm includes five deviant stimuli (225, 250, 500, 800 and 1000Hz) differing in frequencies and presented randomly between the standard stimuli (200Hz). To control for auditory perception, participants were asked to listen to a continuous white noise while wearing earplugs during the entire experiment.

RÉSULTATS - RESULTS

Source reconstruction of vibrotactile event related potentials (ERP) shows a right lateralized evoked response in both somatosensory and auditory regions for the average of all standard stimuli. For the detection of deviant sounds (as compared to standard sounds), two ERPs were observed. The first component was an early positive response around 200ms associated to the deviance detection with generators in the right auditory cortex. This wave was observable only for deviants at 250, 500 and 800Hz but not for the 225 and 1000Hz stimuli. A second positive wave was observed only for deviants at 500, 800 and 1000Hz around 450ms with generators in the dorsal stream.

CONCLUSION

These findings suggest that pitch discrimination without auditory perception is performed by an interplay between tactile and auditory systems but are limited by the frequency discrimination capacities of the tactile system. These results provide a better understanding of multisensory interaction during tactile unisensory perception.

Identifying sex-dependent immune profiles in activated microglia

BACKGROUND: Microglia is the principal immune cells of the brain. Evidence suggests that any changes in their activation profile may significantly alter the outcome of ischemic stroke. However, at present, the molecular mechanisms involved in the control of microglia polarization profiles remain elusive. To add to complexity, increasing evidence suggests marked sexual dimorphism in the processes associated with microglial activation after stroke. To address this question, our project aims to study sex-dependent changes at level of immune cells and then validate the findings in experimental model of stroke specifically targeting on stroke model mimicking female aging since this is a subset of population most susceptible of developing large and serious ischemic lesions. METHODS: In-vitro primary microglia cell cultures, challenged with Lipopolysaccharide (LPS) and Glutamate, were exploited for the assessment of functional and secretory profile using real-time PCR and immunofluorescence, while migration was studied using scratch-wound assay. In vivo, microglial protein expressions were investigated by western blotting techniques following 24 hours of Ischemic stroke in male, female and ovariectomized mice. RESULTS: Our results, in vitro, demonstrate that there is a marked differences in function of microglia. The loss of function was most pronounced in microglial cells isolated from the brains of female mice that were deprived of estrogen (model of menopause). We further investigated the expression profile of these cells at the mRNA level, and we found that microglial cells of aging females developed a distinct immune profile when compare the microglial cells of young females or male cells. CONCLUSION: Our results from both in-vivo and in-vitro suggests that there are sex- (and age) dependent changes in microglial cells, therefore differential therapeutic approaches should be considered for this particular subgroup (menopaused female) that are more suspectable to ischemic stroke.

Sex differences in chloride homeostasis of c-fiber primary afferents in the spinal cord dorsal horn

OBJECTIF - OBJECTIVE

Intracellular Cl- concentration ([Cl-]i) is high in primary sensory neurons due to the activity of the Na+-K+-Cl- cotransporter 1 (NKCC1), causing greater Cl- accumulation than typically seen in CNS neurons. Consequently, central terminals of primary afferents in the spinal dorsal horn experience depolarization upon activation of GABAA receptors (GABAAR). Thus, regulation of [Cl-]i in these terminals may significantly affect transmitter release. Determining the exact [Cl-]i in C-fiber terminals is pivotal to understand sensory processing.

MÉTHODES - METHODS

To image [Cl-]i we used the genetically-encoded ratiometric Cl- sensor, superclomeleon, using 2-photon microscopy in acute spinal cord slices. Superclomeleon was virally transduced selectively in C-fibers in NaV1.8-cre mice. The GABAAR agonist and antagonist muscimol and bicuculline, as well as the NKCC1 antagonist bumetamide, were used to modulate [Cl-]i in afferent terminals in the dorsal horn. NKCC1 mRNA levels in the dorsal root ganglia was evaluated with RNAScope.

RÉSULTATS - RESULTS

We found that [Cl-]i in C-fibers was significantly higher in males than females. Bumetanide significantly decreased [Cl-]i in males but not in females. Bicuculline increased significantly [Cl-]i in C-fibers in females but not in males, indicating more important contribution of tonic GABAA signaling to [Cl-]i in females. NKCC1 mRNA was also significantly lower in females than males, consistent with the functional data.

CONCLUSION

Presynaptic inhibition appear to be under distinct control by GABAergic inhibition between sexes, which should be taken into consideration in future studies.

Neonatal microglia and neurons show distinct molecular signatures following innate immune challenge

OBJECTIVE:

To decipher the microglial-neuronal molecular communication occuring in neonatal mice post an innate immune challenge.

METHODS:

To decipher the microglial-neuronal molecular communication in vivo, we created a transgenic model developed in our lab : NFLrRFPxCD11brGFP mouse, where the ribosomes of microglia and neurons are labelled with appropriate markers. We performed a systemic lipopolysaccharide injection on post-natal day 9 to stimulate immune response. Using modified translational ribosome affinity purification, we took a snapshot of the dynamic translational state of microglial and neuronal ribosomes by capturing the real-time transcribed mRNAs and translated peptides.

 RESULTS:

We identified the top mRNA and protein signatures associated with microglial and neuronal action post LPS challenge. We observed a marked dissociation between upregulated transcripts and peptides, both in microglia as well as neurons,which suggests existence of a post-transcriptional regulation.

CONCLUSION:

Microglia are the primary immune cells of the brain. Comprising of 5-12% of the central nervous system cells, they play an important role in preserving the proper functionality of the brain’s environment.

Neonatal brain is very dynamic, with microglia actively phagocytizing overproduced neurons and weak synapses. An immunological insult can lead to exaggerated microglial response, ultimately damaging the neurons and potentially leading to conditions like autism.  While published studies have been focusing on the identification and description of context-dependent microglia immune transcripts in vivo microglial and neuronal proteomics and associated regulatory mechanisms in neonates are less well defined. One of the limiting factors is lack of appropriate animal models to study real-time in vivo transcriptional and translational dynamics.

Our NFLrRFPxCD11brGFP mouse model containg labelled microglial and neuronal ribosomes enables us to perform translational ribosome affinity purification, thereby allowing us to collect mRNAs as well as peptides from these two cell types. Upon identifying the top mRNA and protein signatures associated with microglial and neuronal action post LPS challenge, we observed a marked dissociation between upregulated transcripts and peptides, both in microglia as well as neurons, suggesting existence of a post-transcriptional regulation. Targeting such regulators may normalize the immune profile by aiding microglial phagocytosis and ultimately bringing homeostasis, thus paving a way to novel therapeutic targets.

MOG-reactive B cells exacerbate the severity of CD4+ T cell-driven CNS autoimmunity

OBJECTIF - OBJECTIVE

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) that has traditionally been considered T cell mediated. However, accumulating evidence points to a crucial role for B cells in disease processes. Experimental autoimmune encephalomyelitis (EAE) is a well-established model to study the immune aspects of CNS autoimmunity. In order to examine the collaboration of B cells and T cells in EAE, we studied non-obese diabetic (NOD)-background IgH[MOG] mice, whose B cells express a transgenic IgH chain derived from a myelin oligodendrocyte glycoprotein (MOG)-specific antibody. Thus, more than 33% of their B cells are specific to the MOG35-55 peptide which enables to study the interaction between B cells and T cells.

MÉTHODES - METHODS

We immunized these IgH[MOG] transgenic mice and NOD wildtype (WT) controls with the MHC class II-restricted peptide MOG35-55, which induces a CD4+ T cell-driven response. We then assessed each mouse every day to evaluate its EAE score and used flow-cytometry to analyze CNS-infiltrating immune cells.

RÉSULTATS - RESULTS

MOG35-55-immunized IgH[MOG] mice rapidly developed severe EAE characterized by leukocytic infiltration and demyelination in the brain, spinal cord and optic nerve. Notably, while the frequency of CD4+ T cells was increased in the CNS of IgH[MOG] with severe disease relative to controls, no differences were observed with respect to the frequency of B cells. Further, IgH[MOG] CNS-infiltrating CD4+ T cells produced significantly higher levels of Th17-associated cytokines GM-CSF and IL-17 compared to those from controls. While looking into CNS-infiltrating B cells, we found that IgH[MOG] B cells compared to NOD B cells produce more Th17-skewing cytokines as IL-6 and IL-23. 

CONCLUSION

IgH[MOG] mice develop a severe EAE upon MOG35-55 immunization. While B cell frequency is stable in the CNS, CD4+ T cells frequency is higher and are skewed into Th17 cells upon B cell signaling. We are now deciphering the cellular and molecular mechanisms in our model that elicit B cells to skew naive T cells into pathogenic Th17 cells.

Impact of alpha-synuclein aggregation on protein degradation systems and its implication in Parkinson’s Disease pathogenesis

OBJECTIF - OBJECTIVE

Parkinson’s Disease (PD) is the second most common neurodegenerative disease in the world. Characterized by motor and non-motor symptoms, PD is associated with the loss of dopaminergic neurons in the Subtantia Nigra (Kalia and Lang, 2015). One of the major pathological hallmarks of the disease is the aggregation of a misfolded protein called alpha-synuclein (a-syn), which will lead to the formation of cellular inclusion known as Lewy bodies (Spillantini et al., 1997). However, how these aggregates disturb neuronal homeostasis leading to neurodegeneration remains elusive. Several studies showed a correlation between alterations of the degradation systems (autophagic or proteasomal), implicated in the protein quality control, and a-syn aggregation (Lehtonen et al., 2019). Nevertheless, it is not clear yet how the degradation is impaired. Our aim is here to know precisely how an alteration of the degradation systems is involved in the pathogenesis of PD. 

MÉTHODES - METHODS

To this purpose, our group recently created a new model in which we control optogenetically and observe in real-time the aggregation of a-syn. This system called the LIPA (Light-Inducible Protein Aggregation) system nicely mimics key features of Lewy bodies (Bérard et al., under review). This system combined with proteasomal and autophagic markers allows us to investigate in vitro how a-syn aggregates impact the degradations systems.

RÉSULTATS - RESULTS

Using this model, we were able to observe for the first time the effect of LIPA-induced aggregates on the proteasome and autophagy systems by using specific markers (Menéndez-Benito et al., 2005). Moreover, we also get interested in the inhibition of proteasomal and autophagic systems and the effect on aggregation.

CONCLUSION

Taken together our observations reveal the ability of our LIPA system to mimic potential effects of a-syn aggregation and the impact of autophagy and proteasome dysfunctions in PD pathogenesis. 

Improving dopaminergic circuit regeneration in Parkinson’s disease using Plxnc1 deficient human induced pluripotent stem cells

Parkinson’s disease (PD) is characterized by the selective degeneration of dopaminergic neurons (DA) of the substantia nigra pars compacta (SNpc). One promising therapeutic strategy for the treatment of PD is cell replacement therapy, where lost DA neurons in SNpc can be replaced with a source of healthy neurons, by means of transplantation. Pre-clinical evidence shows that human induced pluripotent stem cell (hiPSC)-derived DA neurons survive, innervate the host striatum and revert motor asymmetries in preclinical models of PD. However, only a fraction of the graft-derived DA axons reach the functionally relevant dorsal striatum when placed in the midbrain. Our lab has recently revealed that the Sema7a-PlexinC1 guidance pathway controls axon innervation of DA neurons, i.e., SNpc neurons express low levels of PlexinC1 and innervate the dorsal part of the striatum. We thus hypothesize that reduced expression of PlexinC1 in transplanted DA neurons can correct abnormal axonal targeting and lead to increased functional recovery in PD models.

The goal of this study is to generate a hiPSC line where the expression of PlexinC1 has been knockdown (KD) via short hairpin RNA (shRNA) and assess its potential for improved circuitry reconstruction when differentiated into DA neurons and grafted into PD mice models.

First, we tested four putative shRNAs targeted to human PlexinC1, packaged into lentiviral vectors and tagged with GFP, using a shRNA scrambled as control. Their efficiency in knocking down PlexinC1 was validated in human SH-SY5Y using qPCR and Western Blot. The best candidate was then selected for further use in hiPSCs. Next, we generated two stable hiPSC lines (hPlexinC1-shRNA and Scrambled-shRNA) using FACS sorting. The shRNA efficiency and the maintenance of the pluripotent phenotype was validated using qPCR and immunohistochemistry. PlexinC1 KD effect in axon guidance will be assessed in vitro using microfluidics and strip assay.

We have also successfully implemented a hiPSC differentiation protocol optimized for the generation of DA rich transplants in vivo. We are currently planning to start pilot transplantation experiments using the PlexinC1 KD hiPSCs. We expect that our strategy will improve regeneration of DA neurons grafted in SNpc and will efficiently regenerate the nigrostriatal pathway.

Evoked potential correlates of perceptual processing in an analogue trauma paradigm

OBJECTIVE

Previous research suggests that exposure to potentially traumatic events can change the way we process stimuli related to these events, and that differences in the way people encode these events may explain why some people go on to develop post-traumatic disorder while others don’t. However, previous studies have not examined whether visual perception itself is affected by traumatic experiences. Our main objective was to investigate whether experiencing an analogue trauma event facilitates perceptual processing of stimuli related to that event. A secondary objective was to investigate whether priming conceptual or perceptual processing strategies before an analogue trauma event is encoded leads to differences in evoked potentials related to perceptual processing.

METHODS

We recruited 30 participants (7M, 23 F, mean age = 24.2). Participants were split into two groups; we primed conceptual priming in one group and perceptual priming in the other. We then used an analogue trauma paradigm: Participants saw a video showing car accidents and a video presenting clean energy technology, in counterbalanced order. Finally, participants viewed negative and neutral images, some of which were taken from the videos. EEG activity was recorded during picture presentation. We analyzed the amplitude of the P1 evoked potential, which is related to visual perception. Our main analysis was a 2*2*2 ANOVA with encoding style (conceptual, perceptual), valence (negative, neutral) and relatedness (related to the video, unrelated) as independent variables.

RESULTS

P1 amplitude was higher specifically for negative stimuli related to the analogue trauma film (car accidents). Moreover, this result was significant only for participants who underwent perceptual priming before seeing the video.

CONCLUSION

We found evidence of facilitated visual processing of stimuli related to an analogue trauma. This facilitation was weakened when a conceptual mode of encoding was used. While interpretation is limited by reliance on an analogue trauma paradigm, results suggest a possible method for prevention interventions in populations likely to be exposed to potentially traumatic events in the future.

Recovery of the glutamatergic descending drive from the gigantocellular reticular nucleus after spinal cord injury in mice

OBJECTIVE

Following spinal cord injury (SCI), the projections from higher centers are severed, including glutamatergic reticulospinal pathways arising from the gigantocellular reticular nucleus (Gi). Previous studies have shown anatomical plasticity of these reticulospinal pathways after incomplete SCI, however, little is known about their functional plasticity.

METHODS

Using optogenetic tools, kinematics, and electromyographic (EMG) recordings in VGluT2-cre mice, we investigated changes in motor efficacy of glutamatergic Gi neurons following a unilateral SCI. We recorded EMG activity of the ankle flexor Tibialis anterior (TA) and extensor Gastrocnemius lateralis (GL). Short pulses (10 ms) of photostimulations were delivered during treadmill locomotion to probe the ability of the Gi to modify the ongoing locomotor pattern.

RESULTS

Before SCI, photostimulations of the Gi increased activity in muscles during their relaxed phase. After SCI, the excitatory response during locomotion was depressed in the ipsilesional and to a lesser extent in the contralesional TA and GL. Eventually, motor efficacy recovered in the left and right TA and GL. Changes in locomotor performances and motor responses were positively correlated in ipsilesional flexor and extensor muscles, while there were not in contralesional hindlimb muscles. Conditioning glutamatergic Gi neurons also improved spontaneous recovery during voluntary locomotion.

CONCLUSION

In summary, glutamatergic Gi neurons were involved in motor recovery after SCI, thus suggesting that they could be a neurological target to treat patients living with SCI.

In vivo live imaging in mice reveals a day/night cycle regulation of adult neural stem cells activation

OBJECTIVE. New neurons are generated daily in some specific regions of the adult brain through the process of adult neurogenesis. Among these regions is the subventricular zone (SVZ) housing a population of adult neural stem cells (NSCs). Although mostly in a quiescent state, a portion of these NSCs transit daily to a proliferative state, allowing for the production of new neurons and glial cells. However, the dynamic of cell division and cellular mechanisms underlying the transition from the quiescent to the active/proliferative state in the living freely displacing animals are still elusive. METHODS. In this study, we tracked for the first time and for several consecutive days up to several months adult NSCs division in the SVZ of freely behaving mice. We also recorded in vivo NSCs calcium dynamics and optogenetically modulated NSCs Ca2+ dynamics to mimick quiescent NSCs signature. RESULTS. We revealed that NSC division is more frequent during the daylight period. Moreover, manipulation of the day/night cycle, by putting animals in a constant light or darkness, resulted, respectively, in either an increase or a decrease in the percentage of proliferative NSCs. In a search for the mechanisms underlying this phenomenon, we showed that day/night regulation of NSC division is mediated by melatonin signaling which is secreted during the night. The treatment with the melatonin receptors inhibitor before the peaks of melatonin secretion increased the probability of NSCs division during the night. In addition, we showed that quiescent and proliferative NSCs are characterized by different calcium dynamics in vivo and that an optogenetic modulation of Ca2+ dynamics mimicking quiescent NSCs signature was sufficient to prevent NSC from being activated, even in a context of constant day light normally boosting NSCs proliferation. CONCLUSION. NSC division in vivo in freely behaving mice is regulated by the day/night cycle and is dependent on intracellular Ca2+ dynamics.

Stress may explain why a subpopulation of women are at risk of developing cardiorespiratory and metabolic disturbance at menopause

Objective: Elucidate the links between stress and the development of chronic diseases related to cardiorespiratory and metabolic dysfunction.  In women, the prevalence of sleep apnea (SA) rises 3-fold at menopause and main of patients also present hypertension and obesity. Because stress during a critical period of development is a major cause of a range of adult diseases, we tested the hypothesis that stress leads to SA, hypertension, and obesity followed by the loss of ovarian hormones. To do so, we used female rats subjected to neonatal maternal separation (NMS), a translational model of early life stress.

Methodology: Rat pups subjected to NMS were placed in a temperature-controlled incubator 3h/day from postnatal day 3 to 12; controls (CTRL) were undisturbed. At 8 and 40 weeks of age, measurements of ventilation (plethysmography), blood pressure (tail-cuff), and body composition (NMR) were made. We also harvested brains from females with and without ovaries (SHAM versus OVX). Then, we compared the expression of FosB, a transcription factor that indicates neuronal activity, in the paraventricular nucleus of the hypothalamus (PVH), the main structure regulating the stress response.

Results:  NMS does not affect the incidence of SA in females of both ages. At 8 weeks, NMS animals' mean arterial pressure (MAP) was 5% lower than CTRL. In addition, NMS females had 10% more body mass compared to CTRL. At 40 weeks, NMS females were hypertensive (MAP 15% higher than CTRL). In both ages, NMS presented 4% more fat, and 4% less lean tissue. In OVX animals, the expression of FosB in the PVH of NMS was increased compared with other groups (in 55%).

Conclusion: Previous exposure to stress aggravates the physiological impacts of the loss of ovarian function. This supports your hypothesis. The emergence of dysregulation of the stress neuroaxis appears to be an important mechanism to explain those results.

The small GTPase RIT2 acts on the autophagy-lysosome pathway and modulates alpha-synuclein accumulation

OBJECTIF - OBJECTIVE

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. In PD dopaminergic neurons in the substantia nigra pars compacta specifically degenerate and the surviving neurons display accumulations of phosphorylated alpha-synuclein (aSyn) The mechanisms involved in formation, maintenance and degradation of these aggregates are still under intense investigation and the autophagy lysosome pathways (ALP) is a key cellular process hypothesized to be involved in aSyn pathology. Additionally, several PD risk genes have a role in lysosomal biology and autophagy itself. RIT2, a small GTPase, is a novel PD gene risk factor. RIT2 is enriched in rodent substantia nigra pars compacta neurons and is reduced in human PD brains. We are investigating the potential of RIT2 as a novel neuroprotective target and at the same time its physiological role in neurons.

MÉTHODES - METHODS

We used a combination of in vitro cell culture and in vivo experiments to address the neuroprotective effect of the small GTPase RIT2. Specifically, we employed live imaging techniques to investigate different steps of the ALP in vitro. We used different dyes specifically staining autophagosomes, autolysosomes or assessing the proteolytic function of lysosomes in different cell models with modulation of RIT2 expression.

RÉSULTATS - RESULTS

RIT2 mRNA levels are downregulated in the substantia nigra of PD patients, when compared to controls. We observe a downregulation of RIT2 mRNA levels in G2019S-LRRK2 expressing neuroblastoma cells, which display defects in the ALP and pS129-aSyn-positive inclusions. Furthermore, we show that the modulation of RIT2 expression alters several lysosomal phenotypes, like morphology, number and activity. Enhanced RIT2 expression is reducing pS129-aSyn inclusions in vitro and in vivo, validating its neuroprotective effects.

CONCLUSION

Our data indicate that RIT2 acts on the ALP, specifically on the lysosome and aSyn aggregation. Modulating the expression of RIT2 could represent a novel strategy to combat neuropathology in familial and idiopathic PD and possibly in other synucleinopathies.

Behind the key parameters of cellular ion and volume homeostatic capacity

OBJECTIF - OBJECTIVE

There are several evidences that defects in cellular ion and volume homeostatic capacity (CIVHC) can be involved in the pathophysiology of various neuropsychiatric disorders including major depression disorder, bipolar disorders and schizophrenia. The evaluation of ionic and volumetric homeostatic capacity of cells collected from patients in several experimental paradigms therefore represents a strategy to identify the specific cellular phenotype of these disorders. To this end, we aim to develop an in silico mathematical model.

MÉTHODES - METHODS

• We first need experimental data about CIVHC measuring from human cells collected from patients and healthy controls. Experimental measurements are carried out on cells collected from two groups (resilient vs. non-resilient to depression) of Nunavik Inuit involved in the Quanuilirpitaa 2017 health survey. Intracellular ionic concentrations and volume are measured by a multimodal digital holographic imaging technique developed in-house at CERVO Brain Research Centre.
• We intend to develop a simple model which can describe ion and water movement across a membrane. 
• The experimental data will be used to both correctly calibrate the model and identify the key parameters of CIVHC.

RÉSULTATS - RESULTS

Simple two-compartment models of ions transports have been developed to find the key parameters behind homeostasis. Those models are derived by a probabilistic approach. Interestingly, a theoretical study pointed out that, given some set of parameters, those two compartment models have a unique steady state.

CONCLUSION

Mathematical models can be used not only to identify disease-specific phenotypes, but also to understand and obtain genuine improvements in the understanding of the key parameters behind homeostasis. Although it may be possible to calibrate the model output to given experimental data, the study of the model at steady state and in complex dynamic system is of great importance to ensure that the parameters represent those that can be found in an actual physiological system.

DÉLÉTION DE TAU DANS UN MODÈLE MURIN DE LA MALADIE D’HUNTINGTON

Tau est une protéine qui stabilise et régule la dynamique des microtubules en condition physiologique. Une série de publications ont fourni des évidences que la maladie de Huntington (MH) – maladie neurodégénérative autosomique dominante caractérisée par des problèmes moteurs, cognitifs et psychiatriques – peut être une tauopathie – sous-classe de maladies neurodégénératives caractérisées par le dépôt de protéines tau phosphorylées dans le tissu cérébral – en révélant que (i) des agrégats de tau se retrouvent dans plusieurs structures cérébrales de patients atteints de MH et (ii) les déficits comportementaux moteurs peuvent être améliorés avec une délétion de tau chez un modèle de souris transgénique de MH.

OBJECTIFS. Les objectifs sont donc d'étudier l’évolution des déficits associés à la MH en présence ou en l'absence de tau.

METHODES. Ce projet repose sur l'utilisation d’un modèle murin; zQ175/mTKO – modèle MH dont la protéine tau a été délétée (mTKO). Des tests comportementaux tels que le labyrinthe de Barnes, le champ ouvert, le test de la poutre et le rotarod sont en cours sur 4 génotypes issus de ce croisement; wild-type (wt)/wt, wt/mTKO, zQ175/wt et zQ175/mTKO. Ces tests sont réalisés à 3, 6, 9 et 12 mois dans le but d'évaluer les conséquences de l’absence de tau sur le comportement de souris MH. Des analyses post-mortem associées à la maladie sont prévues telles que la quantification des niveaux de protéines mutées et des agrégats formés, la neuroinflammation, l’organisation des microtubules et la dégénérescence cellulaire afin de comprendre les résultats comportementaux obtenus.

RESULTATS. Les résultats préliminaires obtenus dans le modèle zQ175/mTKO suggèrent une précipitation des déficits moteurs– tels que vu par le test de la poutre et cognitifs – tels qu’observés par le test du labyrinthe de Barnes – chez les souris zQ175 délétées en tau. De plus, les tests comportementaux du champ ouvert et de rotarod montrent une aggravation des déficits moteurs et cognitifs chez les souris zQ175/mTKO. Ces résultats démontrent une relation importante entre mHtt et tau.

CONCLUSION. Nos résultats révèlent que l'absence de tau cause une précipitation et exacerbation des déficits cognitifs et moteurs chez les souris zQ175/mTKO. Des études plus approfondies permettront une meilleure compréhension des relations entre la protéine tau, la mHtt et le développement des déficits comportementaux dans la MH.

Être forcé de quitter son pays: impact sur la mémoire

OBJECTIF. Les individus qui fuient leur pays ont souvent été exposés à un grand nombre d’évènements traumatiques, ce qui peut mener à des symptômes de trouble de stress post-traumatique (TSPT), mais aussi à une altération de certaines fonctions cognitives, comme la mémoire autobiographique. En effet, les gens souffrant de TSPT semblent parfois présenter des difficultés à se souvenir d’évènements personnels liés à une occasion spécifique. L’objectif est d’observer l’impact de l’exposition traumatique et des symptômes de TSPT vécus par les personnes réfugiées sur leur mémoire autobiographique. Le deuxième objectif était d’examiner la différence entre la spécificité de souvenirs positifs vs des souvenirs négatifs.

MÉTHODES. Nous avons mesuré la capacité de mémoire autobiographique de 25 personnes réfugiées. Nous avons présenté 10 mots-clés (5 positifs et 5 négatifs), puis avons demandé de raconter un souvenir spécifique relié à chaque mot. Ensuite, nous avons calculé leur pourcentage de souvenirs spécifique.

RÉSULTATS. Pour les souvenirs négatifs, chez les réfugiés de guerre, on retrouve une relation positive entre le degré de spécificité des souvenirs racontés et la sévérité des symptômes traumatiques : r = 0,71, p = 0,009. Cette relation est absente chez les réfugiés politiques, et pour les souvenirs positifs.  

CONCLUSION. Les réfugiés de guerre démontrent un profil de mémoire différent des réfugiés politiques. Les réfugiés de guerre qui rapportent plus de symptômes traumatiques récupèrent de façon plus spécifique les souvenirs négatifs. Le niveau d’exposition traumatique et la sévérité des symptômes traumatiques semblent donc avoir un impact sur le biais à récupérer avec plus de détails les souvenirs négatifs.

Évaluation des troubles acquis de la communication à la suite d'un événement neurologique : Étude de besoins auprès de la Nation Atikamekw

L’aphasie et le trouble cognitivo-communicationnel sont des troubles acquis de la communication (TAC) pouvant survenir à la suite d’un événement neurologique (ex. : accident vasculaire cérébral (AVC), traumatisme crânien (TCC), maladie neurodégénérative). L’évaluation des TAC est essentielle afin de diriger la rééducation orthophonique. Au Canada, bien que l’incidence des AVC et des TCC soit plus élevée chez les Premières Nations (PN) par rapport au reste de la population, aucun outil adapté à eux n’existe. La Nation Atikamekw (NA) est parmi les PN du Canada où une langue autochtone est dominante. En effet, les membres de cette Nation sont majoritairement bilingues atikamekw-français. Comme il n’existe pas d’outils orthophoniques dans ces langues, les atikamekw sont évalués à l’aide d’outils non adaptés n’assurant pas de résultats fiables. Cela peut avoir un impact négatif sur la rééducation orthophonique subséquente. Objectif. Bien que la finalité de cette démarche soit la création d’un outil d’évaluation orthophonique culturellement adapté et bilingue français-atikamekw, il faut comprendre les besoins de la NA avant de pouvoir développer un outil adapté à elle. Ainsi, l’objectif principal de ce projet est la réalisation d’une étude de besoins (en cours) pour connaître la réalité et les besoins dans l’évaluation des TAC chez la NA. Méthodes. Des entrevues semi-dirigées seront réalisées auprès de 1) un membre du Conseil de bande de chaque communauté atikamekw et 2) un professionnel de la santé travaillant dans le centre de santé de chaque communauté. En parallèle, des questionnaires seront envoyés à des orthophonistes travaillant auprès des membres de la NA. Ceux-ci auront pour but de détailler la pratique de ces orthophonistes auprès des membres de la NA ayant un TAC et de déterminer leurs besoins à cet égard. Un échantillon de 20 personnes est visé. Des analyses qualitatives seront réalisées à l’aide du logiciel QDA Miner. Résultats. Il est attendu que l’étude permette d’obtenir les bases nécessaires à la création d’un outil adapté à la NA. Conclusion. Ce projet permet des avancées cliniques et sensibilise la communauté scientifique à la richesse culturo-linguistique de la NA.